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Spindle ApparatusNuclear Matrix-Associated ProteinsMitosisMicrotubulesCentrosomeChromosome SegregationTubulinMeiosisMuscle SpindlesGolgi ApparatusCell Cycle ProteinsFluorescent Antibody TechniqueHeLa CellsMolecular Sequence DataAnaphaseKinetochoresMetaphaseKinesinMicrotubule-Associated ProteinsNocodazoleMad2 ProteinsAurora KinasesChromosomesDyneinsTelophaseM Phase Cell Cycle CheckpointsCytokinesisMicroscopy, FluorescenceOocytesProtein-Serine-Threonine KinasesMicrotubule-Organizing CenterSaccharomyces cerevisiae ProteinsMicrotubule ProteinsMutationMicroscopy, ElectronNuclear ProteinsMotor Neurons, GammaCentriolesCell CycleProphaseSaccharomyces cerevisiaePrometaphaseOrganoidsCentromereCell PolarityBirefringenceProtein TransportCdc20 Proteinsran GTP-Binding ProteinAmino Acid SequenceInterphaseXenopus Proteins
Spindle Apparatus: A microtubule structure that forms during CELL DIVISION. It consists of two SPINDLE POLES, and sets of MICROTUBULES that may include the astral microtubules, the polar microtubules, and the kinetochore microtubules.Nuclear Matrix-Associated Proteins: A broad category of nuclear proteins that are components of or participate in the formation of the NUCLEAR MATRIX.Mitosis: A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species.Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein TUBULIN and are influenced by TUBULIN MODULATORS.Centrosome: The cell center, consisting of a pair of CENTRIOLES surrounded by a cloud of amorphous material called the pericentriolar region. During interphase, the centrosome nucleates microtubule outgrowth. The centrosome duplicates and, during mitosis, separates to form the two poles of the mitotic spindle (MITOTIC SPINDLE APPARATUS).Chromosome Segregation: The orderly segregation of CHROMOSOMES during MEIOSIS or MITOSIS.Tubulin: A microtubule subunit protein found in large quantities in mammalian brain. It has also been isolated from SPERM FLAGELLUM; CILIA; and other sources. Structurally, the protein is a dimer with a molecular weight of approximately 120,000 and a sedimentation coefficient of 5.8S. It binds to COLCHICINE; VINCRISTINE; and VINBLASTINE.Meiosis: A type of CELL NUCLEUS division, occurring during maturation of the GERM CELLS. Two successive cell nucleus divisions following a single chromosome duplication (S PHASE) result in daughter cells with half the number of CHROMOSOMES as the parent cells.Muscle Spindles: Skeletal muscle structures that function as the MECHANORECEPTORS responsible for the stretch or myotactic reflex (REFLEX, STRETCH). They are composed of a bundle of encapsulated SKELETAL MUSCLE FIBERS, i.e., the intrafusal fibers (nuclear bag 1 fibers, nuclear bag 2 fibers, and nuclear chain fibers) innervated by SENSORY NEURONS.Golgi Apparatus: A stack of flattened vesicles that functions in posttranslational processing and sorting of proteins, receiving them from the rough ENDOPLASMIC RETICULUM and directing them to secretory vesicles, LYSOSOMES, or the CELL MEMBRANE. The movement of proteins takes place by transfer vesicles that bud off from the rough endoplasmic reticulum or Golgi apparatus and fuse with the Golgi, lysosomes or cell membrane. (From Glick, Glossary of Biochemistry and Molecular Biology, 1990)Cell Cycle Proteins: Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.Fluorescent Antibody Technique: Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.HeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Anaphase: The phase of cell nucleus division following METAPHASE, in which the CHROMATIDS separate and migrate to opposite poles of the spindle.Kinetochores: Large multiprotein complexes that bind the centromeres of the chromosomes to the microtubules of the mitotic spindle during metaphase in the cell cycle.Metaphase: The phase of cell nucleus division following PROMETAPHASE, in which the CHROMOSOMES line up across the equatorial plane of the SPINDLE APPARATUS prior to separation.Kinesin: A microtubule-associated mechanical adenosine triphosphatase, that uses the energy of ATP hydrolysis to move organelles along microtubules toward the plus end of the microtubule. The protein is found in squid axoplasm, optic lobes, and in bovine brain. Bovine kinesin is a heterotetramer composed of two heavy (120 kDa) and two light (62 kDa) chains. EC 3.6.1.-.Microtubule-Associated Proteins: High molecular weight proteins found in the MICROTUBULES of the cytoskeletal system. Under certain conditions they are required for TUBULIN assembly into the microtubules and stabilize the assembled microtubules.Nocodazole: Nocodazole is an antineoplastic agent which exerts its effect by depolymerizing microtubules.Mad2 Proteins: Mad2 is a component of the spindle-assembly checkpoint apparatus. It binds to and inhibits the Cdc20 activator subunit of the anaphase-promoting complex, preventing the onset of anaphase until all chromosomes are properly aligned at the metaphase plate. Mad2 is required for proper microtubule capture at KINETOCHORES.Aurora Kinases: A family of highly conserved serine-threonine kinases that are involved in the regulation of MITOSIS. They are involved in many aspects of cell division, including centrosome duplication, SPINDLE APPARATUS formation, chromosome alignment, attachment to the spindle, checkpoint activation, and CYTOKINESIS.Chromosomes: In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)Dyneins: A family of multisubunit cytoskeletal motor proteins that use the energy of ATP hydrolysis to power a variety of cellular functions. Dyneins fall into two major classes based upon structural and functional criteria.Telophase: The final phase of cell nucleus division following ANAPHASE, in which two daughter nuclei are formed, the CYTOPLASM completes division, and the CHROMOSOMES lose their distinctness and are transformed into CHROMATIN threads.M Phase Cell Cycle Checkpoints: The cellular signaling system that halts the progression of cells through MITOSIS or MEIOSIS if a defect that will affect CHROMOSOME SEGREGATION is detected.Cytokinesis: The process by which the CYTOPLASM of a cell is divided.Microscopy, Fluorescence: Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.Oocytes: Female germ cells derived from OOGONIA and termed OOCYTES when they enter MEIOSIS. The primary oocytes begin meiosis but are arrested at the diplotene state until OVULATION at PUBERTY to give rise to haploid secondary oocytes or ova (OVUM).Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.Microtubule-Organizing Center: An amorphous region of electron dense material in the cytoplasm from which the MICROTUBULES polymerization is nucleated. The pericentriolar region of the CENTROSOME which surrounds the CENTRIOLES is an example.Saccharomyces cerevisiae Proteins: Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.Microtubule Proteins: Proteins found in the microtubules.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Microscopy, Electron: Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.Motor Neurons, Gamma: Motor neurons which activate the contractile regions of intrafusal SKELETAL MUSCLE FIBERS, thus adjusting the sensitivity of the MUSCLE SPINDLES to stretch. Gamma motor neurons may be "static" or "dynamic" according to which aspect of responsiveness (or which fiber types) they regulate. The alpha and gamma motor neurons are often activated together (alpha gamma coactivation) which allows the spindles to contribute to the control of movement trajectories despite changes in muscle length.Centrioles: Self-replicating, short, fibrous, rod-shaped organelles. Each centriole is a short cylinder containing nine pairs of peripheral microtubules, arranged so as to form the wall of the cylinder.Cell Cycle: The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.Prophase: The first phase of cell nucleus division, in which the CHROMOSOMES become visible, the CELL NUCLEUS starts to lose its identity, the SPINDLE APPARATUS appears, and the CENTRIOLES migrate toward opposite poles.Saccharomyces cerevisiae: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.Prometaphase: The phase of cell nucleus division following PROPHASE, when the breakdown of the NUCLEAR ENVELOPE occurs and the MITOTIC SPINDLE APPARATUS enters the nuclear region and attaches to the KINETOCHORES.Organoids: An organization of cells into an organ-like structure. Organoids can be generated in culture. They are also found in certain neoplasms.Centromere: The clear constricted portion of the chromosome at which the chromatids are joined and by which the chromosome is attached to the spindle during cell division.Cell Polarity: Orientation of intracellular structures especially with respect to the apical and basolateral domains of the plasma membrane. Polarized cells must direct proteins from the Golgi apparatus to the appropriate domain since tight junctions prevent proteins from diffusing between the two domains.Birefringence: The property of nonisotropic media, such as crystals, whereby a single incident beam of light traverses the medium as two beams, each plane-polarized, the planes being at right angles to each other. (Cline et al., Dictionary of Visual Science, 4th ed)Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.Cdc20 Proteins: Highly conserved proteins that specifically bind to and activate the anaphase-promoting complex-cyclosome, promoting ubiquitination and proteolysis of cell-cycle-regulatory proteins. Cdc20 is essential for anaphase-promoting complex activity, initiation of anaphase, and cyclin proteolysis during mitosis.ran GTP-Binding Protein: A monomeric GTP-binding protein involved in nucleocytoplasmic transport of proteins into the nucleus and RNA into the cytoplasm. This enzyme was formerly listed as EC 3.6.1.47.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Interphase: The interval between two successive CELL DIVISIONS during which the CHROMOSOMES are not individually distinguishable. It is composed of the G phases (G1 PHASE; G0 PHASE; G2 PHASE) and S PHASE (when DNA replication occurs).Xenopus Proteins: Proteins obtained from various species of Xenopus. Included here are proteins from the African clawed frog (XENOPUS LAEVIS). Many of these proteins have been the subject of scientific investigations in the area of MORPHOGENESIS and development.

Drosophila oogenesis: versatile spn doctors. (1/4092)

Recent work on Drosophila oogenesis has uncovered connections between cell-cycle checkpoints and pattern formation. Genes of the spindle class, which encode double-strand break repair enzymes and RNA helicases, affect oocyte polarity and the decision whether to differentiate as an oocyte or a nurse cell.  (+info)

C-myc overexpression and p53 loss cooperate to promote genomic instability. (2/4092)

p53 monitors genomic integrity at the G1 and G2/M cell cycle checkpoints. Cells lacking p53 may show gene amplification as well as the polyploidy or aneuploidy typical of many tumors. The pathways through which this develops, however, are not well defined. We demonstrate here that the combination of p53 inactivation and c-myc overexpression in diploid cells markedly accelerates the spontaneous development of tetraploidy. This is not seen with either N-myc or L-myc. Tetraploidy is accompanied by significantly higher levels of cyclin B and its associated cdc2 kinase activity. Mitotic spindle poisons accelerate the appearance of tetraploidy in cells either lacking functional p53 or overexpressing c-myc whereas the combination is additive. Restoration of p53 function in cells overexpressing c-myc causing rapid apoptosis, indicating that cells yet to become tetraploid have nonetheless suffered irreversible genomic and/or mitotic spindle damage. In the face of normal p53 function, such damage would either be repaired or trigger apoptotis. We propose that loss of p53 and overexpression of c-myc permits the emergence and survival of cells with increasingly severe damage and the eventual development of tetraploidy.  (+info)

Defects in Saccharomyces cerevisiae protein phosphatase type I activate the spindle/kinetochore checkpoint. (3/4092)

A conditional allele of type 1 protein phosphatase (glc7-129) in Saccharomyces cerevisiae causes first cycle arrest in G2/M, characterized by cells with a short spindle and high H1 kinase activity. Point-of-execution experiments indicate Glc7p function is required in G2/M just before anaphase for the completion of mitosis. Loss of the spindle/kinetochore checkpoint in glc7-129 cells abolishes the G2/M cell cycle arrest with a concomitant increase in chromosome loss and reduced viability. These results support a role for Glc7p in regulating kinetochore attachment to the spindle, an event monitored by the spindle/kinetochore checkpoint.  (+info)

The conserved protein kinase Ipl1 regulates microtubule binding to kinetochores in budding yeast. (4/4092)

Chromosome segregation depends on kinetochores, the structures that mediate chromosome attachment to the mitotic spindle. We isolated mutants in IPL1, which encodes a protein kinase, in a screen for budding yeast mutants that have defects in sister chromatid separation and segregation. Cytological tests show that ipl1 mutants can separate sister chromatids but are defective in chromosome segregation. Kinetochores assembled in extracts from ipl1 mutants show altered binding to microtubules. Ipl1p phosphorylates the kinetochore component Ndc10p in vitro and we propose that Ipl1p regulates kinetochore function via Ndc10p phosphorylation. Ipl1p localizes to the mitotic spindle and its levels are regulated during the cell cycle. This pattern of localization and regulation is similar to that of Ipl1p homologs in higher eukaryotes, such as the human aurora2 protein. Because aurora2 has been implicated in oncogenesis, defects in kinetochore function may contribute to genetic instability in human tumors.  (+info)

Abnormal spindle protein, Asp, and the integrity of mitotic centrosomal microtubule organizing centers. (5/4092)

The product of the abnormal spindle (asp) gene was found to be an asymmetrically localized component of the centrosome during mitosis, required to focus the poles of the mitotic spindle in vivo. Removing Asp protein function from Drosophila melanogaster embryo extracts, either by mutation or immunodepletion, resulted in loss of their ability to restore microtubule-organizing center activity to salt-stripped centrosome preparations. This was corrected by addition of purified Asp protein. Thus, Asp appears to hold together the microtubule-nucleating gamma-tubulin ring complexes that organize the mitotic centrosome.  (+info)

Influence of centriole behavior on the first spindle formation in zygotes of the brown alga Fucus distichus (Fucales, Phaeophyceae). (6/4092)

The influence of centrioles, derived from the sperm flagellar basal bodies, and the centrosomal material (MTOCs) on spindle formation in the brown alga Fucus distichus (oogamous) was studied by immunofluorescence microscopy using anti-centrin and anti-beta-tubulin antibodies. In contrast to a bipolar spindle, which is formed after normal fertilization, a multipolar spindle was formed in polyspermic zygote. The number of mitotic poles in polyspermic zygotes was double the number of sperm involved in fertilization. As an anti-centrin staining spot (centrioles) was located at these poles, the multipolar spindles in polyspermic zygotes were produced by the supplementary centrioles. When anucleate egg fragments were fertilized, chromosome condensation and mitosis did not occur in the sperm nucleus. Two anti-centrin staining spots could be detected, microtubules (MTs) radiated from nearby, but the mitotic spindle was never produced. When a single sperm fertilized multinucleate eggs (polygyny), abnormal spindles were also observed. In addition to two mitotic poles containing anti-centrin staining spots, extra mitotic poles without anti-centrin staining spots were also formed, and as a result multipolar spindles were formed. When karyogamy was blocked with colchicine, it became clear that the egg nucleus proceeded independently into mitosis accompanying chromosome condensation. A monoastral spindle could be frequently observed, and in rare cases a barrel-shaped spindle was formed. However, when a sperm nucleus was located near an egg nucleus, the two anti-centrin staining spots shifted to the egg nucleus from the sperm nucleus. In this case, a normal spindle was formed, the egg chromosomes arranged at the equator, and the associated MTs elongated from one pole of the egg spindle toward the sperm chromosomes which were scattered. From these results, it became clear that paternal centrioles derived from the sperm have a crucial role in spindle formation in the brown algae, such as they do during animal fertilization. However, paternal centrioles were not adequate for the functional centrosome during spindle formation. We speculated that centrosomal materials from the egg cytoplasm aggregate around the sperm centrioles and are needed for centrosomal activation.  (+info)

Self assembly of NuMA: multiarm oligomers as structural units of a nuclear lattice. (7/4092)

NuMA is a nuclear matrix protein in interphase and relocates to the spindle poles in mitotis. Different NuMA constructs, in which either N- or C-terminal domains were deleted, and the full-length construct were expressed in Escherichia coli, and the NuMA polypeptides were purified to homogeneity and allowed to assemble in vitro. Electron microscopy showed that NuMA can build multiarm oligomers by interaction of the C-terminal globular domains. Each arm of the oligomer corresponds to a NuMA dimer. Oligomers with up to 10 or 12 arms have been observed for both full-length NuMA and for constructs that still contain the proximal part of the C-terminal tail domain. Other results from this laboratory have shown that transient overexpression of NuMA in HeLa cells induces a nuclear scaffold with a quasi-hexagonal organization that can fill the nuclei. Here we show that computer modelling of the three-dimensional packing of NuMA into such scaffolds can explain the different spacing of the hexagons seen when constructs with different coiled-coil lengths are used. Thus, the 12 arm oligomer, for which we have in vitro evidence, may be the structural unit from which the nuclear scaffold in transfected cells is built.  (+info)

Control of mitotic spindle position by the Saccharomyces cerevisiae formin Bni1p. (8/4092)

Alignment of the mitotic spindle with the axis of cell division is an essential process in Saccharomyces cerevisiae that is mediated by interactions between cytoplasmic microtubules and the cell cortex. We found that a cortical protein, the yeast formin Bni1p, was required for spindle orientation. Two striking abnormalities were observed in bni1Delta cells. First, the initial movement of the spindle pole body (SPB) toward the emerging bud was defective. This phenotype is similar to that previously observed in cells lacking the kinesin Kip3p and, in fact, BNI1 and KIP3 were found to be in the same genetic pathway. Second, abnormal pulling interactions between microtubules and the cortex appeared to cause preanaphase spindles in bni1Delta cells to transit back and forth between the mother and the bud. We therefore propose that Bni1p may localize or alter the function of cortical microtubule-binding sites in the bud. Additionally, we present evidence that other bipolar bud site determinants together with cortical actin are also required for spindle orientation.  (+info)

Loss of MYO5B expression deregulates late endosome size which hinders mitotic spindle orientation - NewsemiaLoss of MYO5B expression deregulates late endosome size which hinders mitotic spindle orientation - Newsemia
by Changsen Leng, Arend W. Overeem, Fernando Cartón-Garcia, Qinghong Li, Karin Klappe, Jeroen Kuipers, Yingying Cui, Inge S. Zuhorn, Diego Arango, Sven C. D. van IJzendoorn. Recycling endosomes regulate plasma membrane recycling. Recently, recycling endosome-associated proteins have been implicated in the positioning and orientation of the mitotic spindle and cytokinesis. Loss of MYO5B, encoding the recycling endosome-associated myosin Vb, is associated with tumor development and tissue architecture defects in the gastrointestinal tract. Whether loss of MYO5B expression affects mitosis is not known. Here, we demonstrate that loss of MYO5B expression delayed cytokinesis, perturbed mitotic spindle orientation, led to the misorientation of the plane of cell division during the course of mitosis, and resulted in the delamination of epithelial cells. Remarkably, the effects on spindle orientation, but not cytokinesis, were a direct consequence of physical hindrance by giant late endosomes, which ...
The checkpoint control for anaphase onset does not monitor excess numbers of spindle poles or bipolar spindle symmetry |...The checkpoint control for anaphase onset does not monitor excess numbers of spindle poles or bipolar spindle symmetry |...
Exit from mitosis in animal cells is substantially delayed when spindle assembly is inhibited, spindle bipolarity is disrupted, or when a monopolar spindle is formed. These observations have led to the proposal that animal cells have a spindle assembly checkpoint for the metaphase-anaphase transition that monitors bipolar spindle organization. However, the existence of such a checkpoint is uncertain because perturbations in spindle organization can produce unattached kinetochores, which by themselves are known to delay anaphase onset. In this study we have tested if cells monitor bipolar spindle organization, independent of kinetochore attachment, by analyzing the duration of mitosis in sea urchin zygotes and vertebrate somatic cells containing multipolar spindles in which all kinetochores are attached to spindle poles. We found that sea urchin zygotes containing tripolar or tetrapolar spindles progressed from nuclear envelope breakdown to anaphase onset with normal timing. We also found that ...
Kinesin-5 Eg5 is essential for spindle assembly and chromosome alignment of mouse spermatocytes | Cell Division | Full TextKinesin-5 Eg5 is essential for spindle assembly and chromosome alignment of mouse spermatocytes | Cell Division | Full Text
Microtubule organization is essential for bipolar spindle assembly and chromosome segregation, which contribute to genome stability. Kinesin-5 Eg5 is known to be a crucial regulator in centrosome separation and spindle assembly in mammalian somatic cells, however, the functions and mechanisms of Eg5 in male meiotic cell division remain largely unknown. In this study, we have found that Eg5 proteins are expressed in mouse spermatogonia, spermatocytes and spermatids. After Eg5 inhibition by specific inhibitors Monastrol, STLC and Dimethylenastron, the meiotic spindles of dividing spermatocytes show spindle collapse and the defects in bipolar spindle formation. We demonstrate that Eg5 regulates spindle bipolarity and the maintenance of meiotic spindles in meiosis. Eg5 inhibition leads to monopolar spindles, spindle abnormalities and chromosome misalignment in cultured GC-2 spd cells. Furthermore, Eg5 inhibition results in the decrease of the spermatids and the abnormalities in mature sperms. Our results
Anastral spindle assembly and γ-tubulin in Drosophila oocytes | BMC Cell Biology | Full TextAnastral spindle assembly and γ-tubulin in Drosophila oocytes | BMC Cell Biology | Full Text
Microtubule nucleation for anastral spindle assembly is dependent on chromatin, differing from astral spindles; however, the mechanism of nucleation is still not certain. The initial stages in formation of anastral Drosophila oocyte MI spindles have been studied by imaging live oocytes injected with rhodamine-tubulin [33] or expressing the kinesin-14 Ncd motor fused to GFP to visualize the spindle [20]. Microtubule growth from the condensed MI chromosomes or karyosome was observed in both cases, providing evidence that microtubule nucleation occurs from chromatin, as first observed in Xenopus extract spindles [1]. Time-lapse images obtained with Ncd-GFP showed small fluorescent foci or asters that migrated towards and associated with the karyosome, after which spindle microtubules grew out in all directions from the chromosomes [20]. The asters were also observed labeled with rhodamine-tubulin but were thought not to play a role in spindle assembly, in part because they were not associated with ...
BIOL1020 Genetics blog: Cortical dynein and RanGTP in Mitotic Spindle OrientationBIOL1020 Genetics blog: Cortical dynein and RanGTP in Mitotic Spindle Orientation
The journal shows that mitotic spindle orientation is powered by cortical dynein and regulated by two signal gradients during mitosis, Plk1 and the RanGTP [3]. However, many things still remain elusive such as the molecular level of how RanGTP interacts with LNG-NuMA and causes it to delocalise off the cell cortex. Understanding still remains underdeveloped, especially of other eukaryotic cells, such as plants, which dont have centrosomes [1]. Greater understanding in these processes and other complementary signals can be applied into targeted therapy and chemotherapy for various diseases [6]. Inhibitors and targeting drugs can provide effective therapeutic applications to cancers, which can target specific cells, important signals (such as Plk1, cortical dynein and LGN-NuMA) and microtubules in different cell cycles of cancerous cells to cause mitotic arrest/death [6]. One of the main goals of anti-mitotics (a branch of chemotherapy drugs) is to disrupt the mitotic spindle. Two common classes ...
Spindle apparatus - WikipediaSpindle apparatus - Wikipedia
In cell biology, the spindle apparatus (or mitotic spindle) refers to the cytoskeletal structure of eukaryotic cells that forms during cell division to separate sister chromatids between daughter cells. It is referred to as the mitotic spindle during mitosis, a process that produces genetically identical daughter cells, or the meiotic spindle during meiosis, a process that produces gametes with half the number of chromosomes of the parent cell. Besides chromosomes, the spindle apparatus is composed of hundreds of proteins. Microtubules comprise the most abundant components of the machinery. Attachment of microtubules to chromosomes is mediated by kinetochores, which actively monitor spindle formation and prevent premature anaphase onset. Microtubule polymerization and depolymerization dynamics drive chromosome congression. Depolymerization of microtubules generates tension at kinetochores; bipolar attachment of sister kinetochores to microtubules emanating from opposite cell poles couples ...
Timely spindle control | Journal of Cell ScienceTimely spindle control | Journal of Cell Science
Formation of the mitotic spindle involves a tightly regulated series of coordinated events that ultimately leads to chromosome segregation and cytokinesis. On p. 435, Stephen Huisman and colleagues investigate the role of the essential cell cycle kinase Cdc28-Clb5 in polarity of the mitotic spindle and describe a novel role for spindle pole body component Spc110 in the regulation of spindle morphogenesis in yeast. The authors performed a genetic screen to identify targets of Cdc28-Clb5 kinase involved in spindle polarity and identified a truncated version of Spc110. The truncated version, Spc110Δ13, can suppress the lethal phenotype of the cdc28-4 clb5Δ strain. Cdc28-Clb5 localises to spindle poles and intranuclear microtubules, which is consistent with a role in spindle morphogenesis. The authors find that the Clb5-dependent kinase phosphorylates Spc110 in a cell-cycle-dependent manner at two CDK consensus sites, which is crucial for correct spindle integrity. Their data support a model ...
Monitoring spindle orientation: Spindle position checkpoint in charge | Cell Division | Full TextMonitoring spindle orientation: Spindle position checkpoint in charge | Cell Division | Full Text
Every cell division in budding yeast is inherently asymmetric and counts on the correct positioning of the mitotic spindle along the mother-daughter polarity axis for faithful chromosome segregation. A surveillance mechanism named the spindle position checkpoint (SPOC), monitors the orientation of the mitotic spindle and prevents cells from exiting mitosis when the spindle fails to align along the mother-daughter axis. SPOC is essential for maintenance of ploidy in budding yeast and similar mechanisms might exist in higher eukaryotes to ensure faithful asymmetric cell division. Here, we review the current model of SPOC activation and highlight the importance of protein localization and phosphorylation for SPOC function.
Microtubule cross-linking activity of She1 ensures spindle stability for spindle positioning | JCBMicrotubule cross-linking activity of She1 ensures spindle stability for spindle positioning | JCB
In conclusion, we propose that the mitotic spindle protein She1 functions as an MT cross-linking protein to maintain proper spindle stability during metaphase (Fig. 6 H). There are three major lines of evidence supporting this conclusion: (1) she1-ΔN89 and she1-ΔN126 cells display dynein-independent spindle defects, (2) She1 cross-links MTs in vitro, and (3) the she1-ΔN126 spindle phenotype is complemented by inactivation of Ipl1/Aurora B or by overexpression of she1-ΔN126. The latter shows that premature loading of Ipl1/Aurora B in metaphase inhibits the spindle stabilization effect of she1-ΔN126. Furthermore, we show that this novel activity of She1 is negatively regulated by Ipl1/CPC translocation during anaphase.. Recent work suggested that, during the establishment of a functional metaphase spindle midzone (Hepperla et al., 2014), passive cross-linking proteins are required to maintain proper bundling within the spindle once ipMTs are aligned along the spindle axis by kinesin-14 ...
Aurora A is involved in central spindle assembly through phosphorylation of Ser 19 in P150Glued | JCBAurora A is involved in central spindle assembly through phosphorylation of Ser 19 in P150Glued | JCB
The mitotic spindle is a highly specialized macromolecular machinery that ensures equal segregation of genetic information between daughter cells during mitosis. The assembly and operation of this complex and very dynamic structure have to be appropriately regulated to avoid generation of aneuploid cells. Numerous signaling molecules participate in this regulation, and they include the Aurora A kinase. Some of the functions of the Aurora A kinase during mitotic spindle assembly are now well established; they operate in G2 when the kinase is recruited to centrosomes. Aurora A participates in centrosome maturation by recruiting NDLE1 (Mori et al., 2007) and TACC3 (Kinoshita et al., 2005). In prometaphase, Aurora A participates in regulation of microtubule dynamics by contributing to the recruitment of factors involved in the dynamic instability of microtubules, including DDA3 (Jang and Fang, 2011), MCAK (Zhang et al., 2008), ch-TOG (De Luca et al., 2008; Asteriti et al., 2011), and KIF2A (Jang et ...
RanGTP is required for meiotic spindle organization and the initiation of embryonic development in Drosophila | Dr. Kim S. McKimRanGTP is required for meiotic spindle organization and the initiation of embryonic development in Drosophila | Dr. Kim S. McKim
RanGTP is important for chromosome-dependent spindle assembly in Xenopus extracts. Here we report on experiments to determine the role of the Ran pathway on microtubule dynamics in Drosophila oocytes and embryos. Females expressing a dominant-negative form of Ran have fertility defects, suggesting that RanGTP is required for normal fertility. This is not, however, because of a defect in acentrosomal meiotic spindle assembly. Therefore, RanGTP does not appear to be essential or sufficient for the formation of the acentrosomal spindle. Instead, the most important function of the Ran pathway in spindle assembly appears to be in the tapering of microtubules at the spindle poles, which might be through regulation of proteins such as TACC and the HURP homolog, Mars. One consequence of this spindle organization defect is an increase in the nondisjunction of achiasmate chromosomes. However, the meiotic defects are not severe enough to cause the decreased fertility. Reductions in fertility occur because ...
Recognizing Chromosomes in Trouble: Association of the Spindle Checkpo by Oliver Kerscher, Luciana B. Crotti et al."Recognizing Chromosomes in Trouble: Association of the Spindle Checkpo" by Oliver Kerscher, Luciana B. Crotti et al.
Spindle checkpoint proteins monitor the interaction of the spindle apparatus with the kinetochores, halting anaphase even if the microtubule attachment of only a single chromosome is altered. In this study, we show that Bub3p of Saccharomyces cerevisiae, an evolutionarily conserved spindle checkpoint protein, exhibits distinct interactions with an altered or defective kinetochore(s). We show for the first time that green fluorescent protein-tagged S. cerevisiae Bub3p (Bub3-GFP) exhibits not only a diffuse nuclear localization pattern but also forms distinct nuclear foci in unperturbed growing and G2/M-arrested cells. As Bub3-GFP foci overlap only a subset of kinetochores, we tested a model in which alterations or defects in kinetochore or spindle integrity lead to the distinct enrichment of Bub3p at these structures. In support of our model, kinetochore-associated Bub3-GFP is enriched upon activation of the spindle checkpoint due to nocodazole-induced spindle disassembly, overexpression of the
Role of Molecular Motors and Maps in Spindle Dynamics and Chromosome S by Viktoriya Syrovatkina"Role of Molecular Motors and Maps in Spindle Dynamics and Chromosome S" by Viktoriya Syrovatkina
Mitosis is a key event in the life of a cell, where duplicated chromosomes are separated into the daughter cells. Defects associated with chromosome segregation can lead to aneuploidy, a hallmark of cancer. Chromosome segregation is achieved by the mitotic spindle, which is composed of microtubules (MTs), motors and microtubule associated protein (MAPs). Motors such as kinesins generate forces within the spindle while MAPs perform functions such as organize the spindle pole and maintain the bipolar spindle. Both motors and MAPs contribute to spindle mechanics. Here I used the relatively simple fission yeast to address how defects in spindle mechanics affect chromosome segregation. The metaphase spindle is maintained at a constant length by an antagonistic force-balance model yet how the regulation of metaphase spindle length contribute to subsequent chromosome segregation remains unexplored. To test the force-balance model, I applied gene deletion and fast microfluidic temperature-control with live-cell
Plk4 and Aurora A cooperate in the initiation of acentriolar spindle assembly in mammalian oocytes | JCBPlk4 and Aurora A cooperate in the initiation of acentriolar spindle assembly in mammalian oocytes | JCB
Although the gradient of Ran-GTP around chromatin is critical to promote spindle formation in the absence of centrosomes in many systems (OConnell and Khodjakov, 2007), it is not essential for formation of the first bipolar meiotic spindle upon meiotic resumption in the acentriolar mouse oocyte, even though it does contribute to the increase in density of microtubules after NEBD (Dumont et al., 2007; Schuh and Ellenberg, 2007). By analyzing the very first events in spindle formation upon NEBD, we find that two protein kinases, Aurora A and Plk4, both contribute to trigger microtubule growth and formation of the first meiotic spindle. Inhibition of either kinase dramatically reduces microtubule growth, leading to a reduction in the velocity of the outward expanding chromosomes that are pushed apart by nascent microtubules as the spindle forms. Plk4 inhibition diminishes microtubule growth upon resumption of meiosis, but bipolar spindle formation does eventually occur in a process that requires ...
Frontiers | Multiple Duties for Spindle Assembly Checkpoint Kinases in Meiosis | Cell and Developmental BiologyFrontiers | Multiple Duties for Spindle Assembly Checkpoint Kinases in Meiosis | Cell and Developmental Biology
Cell division in mitosis and meiosis is governed by evolutionary highly conserved protein kinases and phosphatases, controlling the timely execution of key events such as nuclear envelope breakdown, spindle assembly, chromosome attachment to the spindle and chromosome segregation, and cell cycle exit. In mitosis, the spindle assembly checkpoint (SAC) controls the proper attachment to and alignment of chromosomes on the spindle. The SAC detects errors and induces a cell cycle arrest in metaphase, preventing chromatid separation. Once all chromosomes are properly attached, the SAC-dependent arrest is relieved and chromatids separate evenly into daughter cells. The signaling cascade leading to checkpoint arrest depends on several protein kinases that are conserved from yeast to man. In meiosis, haploid cells containing new genetic combinations are generated from a diploid cell through two specialized cell divisions. Though apparently less robust, SAC control also exists in meiosis. Recently, it has emerged
Spindle Model 1Spindle Model 1
The metaphase spindle is a dynamic bipolar structure crucial for proper chromosome segregation, but how microtubules (MTs) are organized within the bipolar architecture remains controversial. To explore MT organization along the pole-to-pole axis, we simulated meiotic spindle assembly in two dimensions using dynamic MTs, a MT cross-linking force, and a kinesin-5-like motor. The bipolar structures that form consist of antiparallel fluxing MTs, but spindle pole formation requires the addition of a NuMA-like minus-end cross-linker and directed transport of MT depolymerization activity toward minus ends. Dynamic instability and minus-end depolymerization generate realistic MT lifetimes and a truncated exponential MT length distribution. Keeping the number of MTs in the simulation constant, we explored the influence of two different MT nucleation pathways on spindle organization. When nucleation occurs throughout the spindle, the simulation quantitatively reproduces features of meiotic spindles ...
Transforming acidic coiled-coil proteinTransforming acidic coiled-coil protein
Conventional centrosomes are absent from a female meiotic spindle in many animals. Instead, chromosomes drive spindle assembly, but the molecular mechanism of this acentrosomal spindle formation is not well understood. This study screened female sterile mutations for defects in acentrosomal spindle formation in Drosophila female meiosis. One of them, remnants (rem), disrupted bipolar spindle morphology and chromosome alignment in non-activated oocytes. It was found that rem encodes a conserved subunit of Cdc2 (Cks30A). Since Drosophila oocytes arrest in metaphase I, the defect represents a new Cks function before metaphase-anaphase transition. In addition, it was found that the essential pole components, Msps and D-TACC, are often mislocalized to the equator, which may explain part of the spindle defect. The second cks gene cks85A, in contrast, has an important role in mitosis. In conclusion, this study describes a new pre-anaphase role for a Cks in acentrosomal meiotic spindle formation ...
Aneuploid colon cancer cells have a robust spindle checkpoint | EMBO ReportsAneuploid colon cancer cells have a robust spindle checkpoint | EMBO Reports
We show here that CIN colon cancer cells undergo transient mitotic arrest in response to spindle damage. However, the maximum mitotic indices achieved by the CIN cells is lower than that of the MIN cells. Thus, we argue that the aneuploid colon cancer cells examined here have a robust spindle checkpoint. Consistently, it now appears that mutations in known spindle checkpoint genes are extremely rare in human tumours (Cahill et al., 1998, 1999a; Imai et al., 1999; Yamaguchi et al., 1999; Myrie et al., 2000; Sato et al., 2000). The reason for the apparent lack of such mutations may be that they are lethal. Although spindle checkpoint genes are non‐essential in yeast (reviewed in Taylor, 1999) mutations in MAD2 and BUB3 result in embryonic lethality in mice (Dobles et al., 2000; Kalitsis et al., 2000). Furthermore, disrupting Bub1 and Mad2 function accelerates mitotic exit in human cells suggesting that spindle checkpoint function may be required to complete normal somatic cell divisions (Taylor ...
Histone H3K4 methylation regulates deactivation of the spindle assembly checkpoint through direct binding of Mad2<...Histone H3K4 methylation regulates deactivation of the spindle assembly checkpoint through direct binding of Mad2<...
TY - JOUR. T1 - Histone H3K4 methylation regulates deactivation of the spindle assembly checkpoint through direct binding of Mad2. AU - Schibler, Andria. AU - Koutelou, Evangelia. AU - Tomida, Junya. AU - Wilson-Pham, Marenda. AU - Wang, Li. AU - Lu, Yue. AU - Cabrera, Alexa Parra. AU - Chosed, Renee J.. AU - Li, Wenqian. AU - Li, Bing. AU - Shi, Xiaobing. AU - Wood, Richard D.. AU - Dent, Sharon Y R. PY - 2016/5/15. Y1 - 2016/5/15. N2 - Histone H3 methylation on Lys4 (H3K4me) is associated with active gene transcription in all eukaryotes. In Saccharomyces cerevisiae, Set1 is the sole lysine methyltransferase required for mono-, di-, and trimethylation of this site. Although H3K4me3 is linked to gene expression, whether H3K4 methylation regulates other cellular processes, such as mitosis, is less clear. Here we show that both Set1 and H3K4 mutants display a benomyl resistance phenotype that requires components of the spindle assembly checkpoint (SAC), including Bub3 and Mad2. These proteins ...
Mutations in the kinesin-like protein Eg5 disrupting localization to the mitotic spindle | PNASMutations in the kinesin-like protein Eg5 disrupting localization to the mitotic spindle | PNAS
Eg5, a member of the bimC subfamily of kinesin-like microtubule motor proteins, localizes to spindle microtubules in mitosis but not to interphase microtubules. We investigated the molecular basis for spindle localization by transient transfection of Xenopus A6 cells with myc-tagged derivatives of Eg5. Expressed at constitutively high levels from a cytomegalovirus promoter, mycEg5 protein is cytoplasmic throughout interphase, begins to bind microtubules in early prophase, and remains localized to spindle and/or midbody microtubules through mitosis to the end of telophase. Both N- and C-terminal regions of Eg5 are required for this cell-cycle-regulated targeting. Eg5 also contains within its C-terminal domain a sequence conserved among bimC subfamily proteins that includes a potential p34cdc2 phosphorylation site. We show that mutation of a single threonine (T937) within this site to nonphosphorylatable alanine abolishes localization of the mutant protein to the spindle, whereas mutation of T937 ...
Differential Regulation of Anaphase Promoting Complex/Cyclosome Substrates by the Spindle Assembly Checkpoint in Saccharomyces...Differential Regulation of Anaphase Promoting Complex/Cyclosome Substrates by the Spindle Assembly Checkpoint in Saccharomyces...
ORDERED temporal degradation of proteins is an important regulatory mechanism that controls progression through the eukaryotic cell cycle (Reed 2006). The anaphase promoting complex/cyclosome (APC/C) is the E3 subunit of an ubiquitin-conjugating enzyme composed of at least thirteen subunits that targets proteins for proteolysis during the cell cycle (Peters 2006). APC/C function is critical for progression through mitosis where it degrades Pds1 (securin in higher eukaryotic cells) and other substrates to promote anaphase and the exit from mitosis (Pines 2006). APC/C cofactors Cdc20 and Cdh1 are important for conferring substrate specificity during different stages in the cell cycle (Peters 2006). It is unclear, however, how the APC/C chooses substrates for ubiquitylation and the specific role of each subunit in this process (Acquaviva and Pines 2006). The spindle assembly checkpoint (SAC) ensures the formation of a bipolar spindle and proper attachment of kinetochores (Lew and Burke 2003). The ...
Response to Comments on A Centrosome-Independent Role for γ-TuRC Proteins in the Spindle Assembly Checkpoint | ScienceResponse to Comments on "A Centrosome-Independent Role for γ-TuRC Proteins in the Spindle Assembly Checkpoint" | Science
Weaver and Cleveland and Taylor et al. contend that our data on the involvement of the γ-tubulin ring complex (γ-TuRC) in the spindle assembly checkpoint (SAC) can be fully explained by kinetochore-derived checkpoint signaling. We maintain that (i) the interactions of γ-TuRC with Cdc20 and BubR1, and (ii) the activation of SAC by γ-TuRC depletion, in addition to the abrogation of kinetochore-microtubule interactions, argue for a more complex mechanism of SAC signaling.. ...
The BRCA1/BARD1 heterodimer modulates Ran-development mitotic spindle assembly. A mitotic role for BRCA1/BARD1 in tumor...The BRCA1/BARD1 heterodimer modulates Ran-development mitotic spindle assembly. A mitotic role for BRCA1/BARD1 in tumor...
The BRCA1/BARD1 heterodimer modulates Ran-development mitotic spindle assembly. A mitotic role for BRCA1/BARD1 in tumor suppression?
Ring Around the Spindle Checkpoint | Science SignalingRing Around the Spindle Checkpoint | Science Signaling
The molecular role of the centrosome in the spindle checkpoint has been debated for some time. Müller et al. have now identified a function for a subset of core centrosomal proteins, namely their involvement in the spindle checkpoint. γ-tubulin ring proteins are functionally and biochemically integrated into checkpoint control, together with two of the major players in this pathway, BubR1 and Cdc20. However, the function of the γ-tubulin ring components was not linked to centrosome integrity, nor did it require localization to this organelle.. H. Müller, M.-L. Fogeron, V. Lehmann, H. Lehrach, B. M. H. Lange, A centrosome-independent role for γ-TuRC proteins in the spindle assembly checkpoint. Science 314, 654-657 (2006). [Abstract] [Full Text]. ...
A lateral belt of cortical LGN and NuMA guides mitotic spindle movements (...) - ENS - Départment de biologieA lateral belt of cortical LGN and NuMA guides mitotic spindle movements (...) - ENS - Départment de biologie
The cell in the middle exhibits the normal biphasic pattern of spindle rotation (planar alignment/planar maintenance) regulated by the lateral (...)
Mitotic spindle rotation and mode of cell division in the developing telencephalon | PNASMitotic spindle rotation and mode of cell division in the developing telencephalon | PNAS
A current theory for the generation of fate asymmetry is based on the discrete localization of cytoplasmic fate-determining molecules within the mother cell and their unequal distribution to daughter cells during division. The molecules so far identified, such as Notch, Numb, Miranda, Staufen, and Prospero (10, 20, 45, 46), have been shown to exhibit either basal or apical "capping" before division in static studies. Importantly, the fate molecule parcellation model only works in conjunction with variable orientations of the final cleavage plane. Assuming that the localization of fate molecule is fixed, only if the plane of cleavage can be modified can divergent cell fates be generated. If, on the other hand, fate molecules are not tethered in the same intracellular location throughout neurogenesis, or if there are multiple signaling pathways as the late vertical neurogenic divisions suggest, then spindle rotation is an even more critical requirement for modulating mode of division.. The nature ...
PhenoPlasmPhenoPlasm
Colocalization experiments of Pfark-1-GFP with a-tubulin. Fluorescence microscopy of fixed schizont stage transgenic parasites expressing Pfark-1-GFP. A and B. An anti-a-tubulin mAb recognizes discrete foci (red) near DAPI-stained nuclear DNA (blue). The red fluorescent pattern is consistent with early-stage mitotic spindle formation developing from the spindle pole bodies anchored in the nuclear membrane. In colour merge images, the Pfark-1-GFP protein appears to localize at opposite sides of the early mitotic spindle, consistent with a localization at the mitotic spindle poles. C and D. In these two panels the anti-a-tubulin mAb recognizes partly disassembled bipolar mitotic spindles (red) aligned with DAPI-stained nuclear bodies (blue), representing daughter nuclear bodies in the process of completion of nuclear division. The Pfark-1-GFP protein does not appear now to be confined to mitotic spindle poles. A diffuse cytosolic green fluorescence is observable, presumably representing the GFP ...
Induction of apoptosis by an inhibitor of the mitotic kinesin KSP requires both activation of the spindle assembly checkpoint...Induction of apoptosis by an inhibitor of the mitotic kinesin KSP requires both activation of the spindle assembly checkpoint...
The inhibition of KSP causes mitotic arrest by activating the spindle assembly checkpoint. While transient inhibition of KSP leads to reversible mitotic arrest, prolonged exposure to a KSP inhibitor induces apoptosis. Induction of apoptosis by the KSP inhibitor couples with mitotic slippage. Slippag …
Bipolar spindle assembly and failure of chromatin stret | Open-iBipolar spindle assembly and failure of chromatin stret | Open-i
Bipolar spindle assembly and failure of chromatin stretching in oocytes expressing αtub67CP40. A, Drosophila female meiotic spindles were examined by indirect
View source for Fast Microtubule Dynamics in Meiotic Spindles Measured by Single Molecule Imaging: Evidence that the Spindle...View source for Fast Microtubule Dynamics in Meiotic Spindles Measured by Single Molecule Imaging: Evidence that the Spindle...
Original Entry: Peter Foster, AP 225, Fall 2011 [[Image:Dn90fig1.png,thumb,300px, Figure 1, taken from [1].]] [[Image:Dn90fig2.png,thumb,300px, Figure 2, taken from [1].]] [[Image:Dn90fig3.png,thumb,300px, Figure 3, taken from [1].]] [[Image:Dn90fig4.png,thumb,300px, Figure 4, taken from [1].]] ==General Information== Authors: Daniel J. Needleman, Aaron Groen, Ryoma Ohi, Tom Maresca, Leonid Mirny, and Tim Mitchison Publication: Needleman et al. Fast microtubule dynamics in meiotic spindles measured by single molecule imaging: Evidence that the spindle environment does not stabilize microtubules. Molecular Biology of the Cell (2010) vol. 21 (2) pp. 323 ==Summary== The meiotic spindle is a piece of cellular machinery composed of microtubules (which are in turn composed of tubulin subunits) that serves to separate chromosomes during cell division. The spindle is incredibly dense with tubulin, containing a concentration much higher than found in the cytoplasm (~60 uM vs ,1uM). Different ...
Conditional targeting of MAD1 to kinetochores is sufficient to reactivate the spindle assembly checkpoint in metaphase |...Conditional targeting of MAD1 to kinetochores is sufficient to reactivate the spindle assembly checkpoint in metaphase |...
Fidelity of chromosome segregation is monitored by the spindle assembly checkpoint (SAC). Key components of the SAC include MAD1, MAD2, BUB1, BUB3, BUBR1, and MPS1. These proteins accumulate on...
Msps protein is localized to acentrosomal poles to ensure bipolarity of Drosophila meiotic spindlesMsps protein is localized to acentrosomal poles to ensure bipolarity of Drosophila meiotic spindles
The female meiotic spindle is commonly formed in a centrosome-independent manner. Here we report the identification of proteins at acentrosomal poles in the female meiotic spindle of Drosophila. The acentrosomal poles contain at least two proteins, Mini-spindles (Msps) and D-TACC, which are also ass …
When the Genome Plays Dice: Circumvention of the Spindle Assembly Checkpoint and Near-Random Chromosome Segregation in...When the Genome Plays Dice: Circumvention of the Spindle Assembly Checkpoint and Near-Random Chromosome Segregation in...
BackgroundNormal cell division is coordinated by a bipolar mitotic spindle, ensuring symmetrical segregation of chromosomes. Cancer cells, however, occasionally divide into three or more directions. Such multipolar mitoses have been proposed to generate genetic diversity and thereby contribute to clonal evolution. However, this notion has been little validated experimentally.Principal FindingsChromosome segregation and DNA content in daughter cells from multipolar mitoses were assessed by multiphoton cross sectioning and fluorescence in situ hybridization in cancer cells and non-neoplastic transformed cells. The DNA distribution resulting from multipolar cell division was found to be highly variable, with frequent nullisomies in the daughter cells. Time-lapse imaging of H2B/GFP-labelled multipolar mitoses revealed that the time from the initiation of metaphase to the beginning of anaphase was prolonged and that the metaphase plates often switched polarity several times before metaphase-anaphase
Role of CENP-A NAC/CAD network in spindle assembly and spindle checkpoint - Research CollectionRole of CENP-A NAC/CAD network in spindle assembly and spindle checkpoint - Research Collection
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Molecular mechanisms of spindle function - Semantic ScholarMolecular mechanisms of spindle function - Semantic Scholar
The key molecules involved in regulating the assembly and function of the mitotic spindle are shared by evolutionarily divergent species. Studies in different model systems are leading to convergent conclusions about the central role of microtubule nucleation and dynamics and of kinesin-related motor proteins in spindle function.
mdf-2 - HORMA domain-containing protein - Caenorhabditis elegans - mdf-2 gene & proteinmdf-2 - HORMA domain-containing protein - Caenorhabditis elegans - mdf-2 gene & protein
centrosome, condensed chromosome kinetochore, condensed nuclear chromosome kinetochore, cytoplasm, kinetochore, nucleoplasm, pronucleus, spindle midzone, embryo development ending in birth or egg hatching, mitotic spindle assembly checkpoint
Loss of the canonical spindle orientation function in the Pins/LGN homolog (...) - ENS - Départment de biologieLoss of the canonical spindle orientation function in the Pins/LGN homolog (...) - ENS - Départment de biologie
Abstract In many cell types, mitotic spindle orientation relies on the canonical LGN complex composed of Pins/LGN, Mud/NuMA, and Gαi subunits. (...)
Dependence of Paclitaxel Sensitivity on a Functional Spindle Assembly Checkpoint<...Dependence of Paclitaxel Sensitivity on a Functional Spindle Assembly Checkpoint<...
TY - JOUR. T1 - Dependence of Paclitaxel Sensitivity on a Functional Spindle Assembly Checkpoint. AU - Sudo, Tamotsu. AU - Nitta, Masayuki. AU - Saya, Hideyuki. AU - Ueno, Naoto T.. PY - 2004/4/1. Y1 - 2004/4/1. N2 - Paclitaxel stabilizes microtubules, causing mitotic arrest and activating the spindle assembly checkpoint. We determined whether suppression of the checkpoint genes Mad2 and BubR1 affects paclitaxel resistance and whether overexpression of Mad2 protein in checkpoint-defective cells enhances paclitaxel sensitivity. Suppression of Mad2 and BubR1 in paclitaxel-treated cancer cells abolished checkpoint function, resulting in paclitaxel resistance that correlated with suppression of cyclin-dependent kinase-1 activity. In contrast, overexpression of Mad2 in cells with a checkpoint defect attributable to low Mad2 expression restored checkpoint function, resulting in enhanced paclitaxel sensitivity that correlated with enhanced cyclin-dependent kinase-1 activity. However, overexpression of ...
MAD1-dependent recruitment of CDK1-CCNB1 to kinetochores promotes spindle checkpoint signaling | Journal of Cell Biology |...MAD1-dependent recruitment of CDK1-CCNB1 to kinetochores promotes spindle checkpoint signaling | Journal of Cell Biology |...
In eukaryotic cells, accurate chromosome segregation requires the spindle assembly checkpoint, a surveillance system monitoring kinetochore attachment to microtubules of the mitotic spindle (Lara-Gonzalez et al., 2012; Musacchio, 2015). The spindle checkpoint kinase MPS1 binds to unattached kinetochores and phosphorylates kinetochore proteins, thus directing the accumulation of spindle checkpoint proteins of the MAD and BUB families (Musacchio, 2015; Ciliberto and Hauf, 2017). A subset of the MAD and BUB proteins then assemble into the mitotic checkpoint complex (MCC; Musacchio, 2015). The mitotic checkpoint complex then diffuses away from the kinetochore to inhibit the ubiquitin E3 ligase anaphase promoting complex/cyclosome (APC/C), thus preventing mitotic exit (Sivakumar and Gorbsky, 2015). The two crucial targets ubiquitylated by the APC/C to promote mitotic exit are securin, the inhibitor of separase, and most important for this work, cyclin B, the activating subunit of a cyclin-dependent ...
Drosophila gene families: Centromeric and Kinetochore ProteinsDrosophila gene families: Centromeric and Kinetochore Proteins
In oocytes, where centrosomes are absent, the chromosomes direct the assembly of a bipolar spindle. Interactions between chromosomes and microtubules are essential for both spindle formation and chromosome segregation. This study examined oocytes lacking two kinetochore proteins, NDC80 and SPC105R, and a centromere-associated motor protein, CENP-E, to characterize the impact of kinetochore-microtubule attachments on spindle assembly and chromosome segregation in Drosophila oocytes. The initiation of spindle assembly was shown to result from chromosome-microtubule interactions that are kinetochore-independent. Stabilization of the spindle, however, depends on both central spindle and kinetochore components. This stabilization coincides with changes in kinetochore-microtubule attachments and bi-orientation of homologs. It is proposed that the bi-orientation process begins with the kinetochores moving laterally along central spindle microtubules towards their minus ends. This movement depends on ...
JAM-A regulates cortical dynein localization through Cdc42 to control planar spindle orientation during mitosis | SFB 829JAM-A regulates cortical dynein localization through Cdc42 to control planar spindle orientation during mitosis | SFB 829
Abstract. Planar spindle orientation in polarized epithelial cells depends on the precise localization of the dynein-dynactin motor protein complex at the lateral cortex. The contribution of cell adhesion molecules to the cortical localization of the dynein-dynactin complex is poorly understood. Here we find that junctional adhesion molecule-A (JAM-A) regulates the planar orientation of the mitotic spindle during epithelial morphogenesis. During mitosis, JAM-A triggers a transient activation of Cdc42 and PI(3)K, generates a gradient of PtdIns(3,4,5)P3 at the cortex and regulates the formation of the cortical actin cytoskeleton. In the absence of functional JAM-A, dynactin localization at the cortex is reduced, the mitotic spindle apparatus is misaligned and epithelial morphogenesis in three-dimensional culture is compromised. Our findings indicate that a PI(3)K- and cortical F-actin-dependent pathway of planar spindle orientation operates in polarized epithelial cells to regulate epithelial ...
Plk1 bound to Bub1 contributes to spindle assembly checkpoint activity during mitosis<...Plk1 bound to Bub1 contributes to spindle assembly checkpoint activity during mitosis<...
TY - JOUR. T1 - Plk1 bound to Bub1 contributes to spindle assembly checkpoint activity during mitosis. AU - Ikeda, Masanori. AU - Tanaka, Kozo. N1 - Funding Information: The authors thank K. Mizuno for YFP-Plk1, J.G. Deluca for Hec1-GFP, M. Lampson for mCherry-Knl1 and Hec1-mCherry-Plk1, G.J. Kops for anti-phospho-Mps1 antibody against T676 and anti-phospho-BubR1 antibody against T680, Y. Watanabe for anti-phospho-Knl1 antibody against T875 and T. Hirota for mCherry-Mis12. We also thank members of the K.T. laboratory for discussions and A. Harata for technical assistance. This work was supported by JSPS KAKENHI Grant Numbers 24370078, 26640067, 26870054, 15H04368, and 16K14604; MEXT KAKENHI Grant Numbers 24114502 and 26114702; and grants from the Takeda Science Foundation, Princess Takamatsu Cancer Research Fund (10-24210).. PY - 2017/12/1. Y1 - 2017/12/1. N2 - For faithful chromosome segregation, the formation of stable kinetochore-microtubule attachment and its monitoring by the spindle ...
MAD2L2 - Mitotic spindle assembly checkpoint protein MAD2B - Homo sapiens (Human) - MAD2L2 gene & proteinMAD2L2 - Mitotic spindle assembly checkpoint protein MAD2B - Homo sapiens (Human) - MAD2L2 gene & protein
Adapter protein able to interact with different proteins and involved in different biological processes. Mediates the interaction between the error-prone DNA polymerase zeta catalytic subunit REV3L and the inserter polymerase REV1, thereby mediating the second polymerase switching in translesion DNA synthesis. Translesion DNA synthesis releases the replication blockade of replicative polymerases, stalled in presence of DNA lesions. May also regulate another aspect of cellular response to DNA damage through regulation of the JNK-mediated phosphorylation and activation of the transcriptional activator ELK1. Inhibits the FZR1- and probably CDC20-mediated activation of the anaphase promoting complex APC thereby regulating progression through the cell cycle. Regulates TCF7L2-mediated gene transcription and may play a role in epithelial-mesenchymal transdifferentiation.
BRK1, a Bub1-Related Kinase, Is Essential for Generating Proper Tension between Homologous Kinetochores at Metaphase I of Rice...BRK1, a Bub1-Related Kinase, Is Essential for Generating Proper Tension between Homologous Kinetochores at Metaphase I of Rice...
In the mitotic cell cycle, it is only when all chromosomes have appropriately established bipolar attachment to the mitotic spindle that the metaphase-to-anaphase transition can occur (Chen, 2004; Yu and Tang, 2005). Because kinetochores capture microtubules in a stochastic manner, three types of erroneous kinetochore attachments, including monotelic (only one of the sister kinetochores is attached to one spindle pole), syntelic (both sister kinetochores are attached to the same spindle pole), and merotelic (one kinetochore is attached to two opposing spindle poles) attachment, frequently occur (Gregan et al., 2011). Thus, there must be a surveillance mechanism that prevents the precocious separation of sister chromatids until all the improper kinetochore attachments are corrected, ensuring the fidelity of chromosome segregation (Meraldi and Sorger, 2005; Yu and Tang, 2005). The spindle assembly checkpoint (SAC) is such a mechanism that delays anaphase onset when any kinetochore is not properly ...
Cytotoxicity of Paclitaxel in Breast Cancer Is due to Chromosome Missegregation on Multipolar Spindles | Science Translational...Cytotoxicity of Paclitaxel in Breast Cancer Is due to Chromosome Missegregation on Multipolar Spindles | Science Translational...
The blockbuster chemotherapy drug paclitaxel is widely presumed to cause cell death in tumors as a consequence of mitotic arrest, as it does at concentrations routinely used in cell culture. However, we determine here that paclitaxel levels in primary breast tumors are well below those required to elicit sustained mitotic arrest. Instead, cells in these lower concentrations of drug proceed through mitosis without substantial delay and divide their chromosomes on multipolar spindles, resulting in chromosome missegregation and cell death. Consistent with these cell culture data, most mitotic cells in primary human breast cancers contain multipolar spindles after paclitaxel treatment. Contrary to the previous hypothesis, we find that mitotic arrest is dispensable for tumor regression in patients. These results demonstrate that mitotic arrest is not responsible for the efficacy of paclitaxel, which occurs because of chromosome missegregation on highly abnormal, multipolar spindles. This mechanistic ...
Central spindle | definition of central spindle by Medical dictionaryCentral spindle | definition of central spindle by Medical dictionary
Looking for online definition of central spindle in the Medical Dictionary? central spindle explanation free. What is central spindle? Meaning of central spindle medical term. What does central spindle mean?
Pins is not required for spindle orientation in the Drosophila wing disc | DevelopmentPins is not required for spindle orientation in the Drosophila wing disc | Development
In animal cells, mitotic spindles are oriented by the dynein/dynactin motor complex, which exerts a pulling force on astral microtubules. Dynein/dynactin localization depends on Mud/NUMA, which is typically recruited to the cortex by Pins/LGN. In Drosophila neuroblasts, the Inscuteable/Baz/Par-6/aPKC complex recruits Pins apically to induce vertical spindle orientation, whereas in epithelial cells, Dlg recruits Pins laterally to orient the spindle horizontally. Here we investigate division orientation in the Drosophila imaginal wing disc epithelium. Live imaging reveals that spindle angles vary widely during prometaphase and metaphase, and therefore do not reliably predict division orientation. This finding prompted us to re-examine mutants that have been reported to disrupt division orientation in this tissue. Loss of Mud/NUMA misorients divisions, but Inscuteable expression and aPKC, dlg and pins mutants have no effect. Furthermore, Mud localizes to the apical-lateral cortex of the wing ...
Spindle assembly checkpoint and its regulators in meiosis. - Semantic ScholarSpindle assembly checkpoint and its regulators in meiosis. - Semantic Scholar
BACKGROUND Meiosis is a unique form of cell division in which cells divide twice but DNA is duplicated only once. Errors in chromosome segregation during meiosis will result in aneuploidy, followed by loss of the conceptus during pregnancy or birth defects. During mitosis, cells utilize a mechanism called the spindle assembly checkpoint (SAC) to ensure faithful chromosome segregation. A similar mechanism has been uncovered for meiosis in the last decade, especially in the past several years. METHODS For this review, we included data and relevant information obtained through a PubMed database search for all articles published in English from 1991 through 2011 which included the term meiosis, spindle assembly checkpoint, or SAC. RESULTS There are 91 studies included. Evidence for the existence of SAC functions in meiosis is provided by studies on the SAC proteins mitotic-arrest deficient-1 (Mad1), Mad2, budding uninhibited by benzimidazole-1 (Bub1), Bub3, BubR1 and Mps1; microtubule-kinetochore
The yeast centrosome translates the positional information of the anaphase spindle into a cell cycle signal | Journal of Cell...The yeast centrosome translates the positional information of the anaphase spindle into a cell cycle signal | Journal of Cell...
The SPOC regulates the phosphorylation of Bfa1 by Cdc5 at SPBs. (A and B) DYN1 CDC5-GFP and dyn1Δ CDC5-GFP cells in anaphase with a correctly aligned or misoriented anaphase spindle were analyzed by fluorescence microscopy. (A) Measurement of the relative fluorescence intensity of the Cdc5-GFP SPB signal of DYN1 CDC5-GFP cells with a correctly aligned anaphase spindle and dyn1Δ CDC5-GFP cells with the anaphase spindle misaligned in the mother cell body. The signals associated with the preexisting old (orange) and new (blue) SPBs were measured. (B) Cdc5-GFP signal at SPBs of DYN1 CDC5-GFP and dyn1Δ CDC5-GFP cells. Spc42-eqFP611 was used as an SPB marker. Note that Spc42-eqFP611 labeled the old SPB in the mother cell body more strongly because of a delay in the folding of the eqFP611 molecule (Pereira et al., 2001; Wiedenmann et al., 2002). DNA was stained with DAPI. (C) CDC5 and cdc5-10 cells were synchronized in G1 with α factor at 23°C and released at 37°C, the restrictive temperature of ...
Title page for ETD etd-06102011-075914Title page for ETD etd-06102011-075914
Each mitotic chromosome is constituted by two sister chromatids whose correct segregation to the daughter cells is ensured by amphitelic attachment, in which the two sister kinetochores (KTs) are attached to microtubules (MTs) from opposite mitotic spindle poles. KT mis-attachments can occur in early mitosis and cause chromosome mis-segregation and aneuploidy if not corrected. These mis-attachments include monotelic (one attached and one unattached sister KT), syntelic (both sister KTs attached to the same spindle pole), and merotelic (a single KT attached to MTs from opposite spindle poles) attachments. A biochemical pathway named the Spindle Assembly Checkpoint (SAC) is responsible for delaying anaphase onset to allow correction of KT mis-attachments. SAC activation is believed to occur due to KT localization of certain SAC proteins and/or lack of tension, but only monotelic attachment has been proven to activate the SAC. To determine if and how other KT mis-attachments may activate the SAC, ...
Sirt1 Regulates Microtubule Dynamics Through Negative Regulation of Plk1 in Mitosis<...Sirt1 Regulates Microtubule Dynamics Through Negative Regulation of Plk1 in Mitosis<...
TY - JOUR. T1 - Sirt1 Regulates Microtubule Dynamics Through Negative Regulation of Plk1 in Mitosis. AU - Kim, Jin Ju. AU - Gil, Na Yeon. AU - Zhang, Xiang Hua. AU - Chun, Kwang Hoon. AU - Fang, Guowei. AU - Kim, Joon. AU - Cho, Hyeseong. AU - Jang, Chang Young. AU - Cha, Hyuk Jin. PY - 2015/9/1. Y1 - 2015/9/1. N2 - Although loss of Sirt1 leads to chromosome aneuploidy, which accounts for higher tumor susceptibility, the molecular mechanisms remain unclear. Herein, we demonstrate that Sirt1 directly regulates Plk1, of which activity is critical for mitotic progression and spindle dynamics. Depletion or inhibition of Sirt1 significantly perturbs the formation of the mitotic spindle, leading to defective chromosome segregation. Elevated depolymerization of the mitotic spindle following loss of Sirt1 was associated with the deregulation of Plk1 activity. Thus, we conclude that Sirt1 may contribute to a mitotic regulator that controls spindle dynamics through Plk1 activity, resulting in fine-tuning ...
Place Spindle Here | Science SignalingPlace Spindle Here | Science Signaling
Nonpolarized cultured cells that adhere to the substrate on which they are growing orient their spindles parallel to the substratum, thereby allowing both daughter cells to maintain contact with the substrate. Interactions between the astral microtubules and various microtubule-organizing proteins, including the minus end-directed motor complex and the dynein-dynactin complex, are involved in connecting the spindle to the actin cytoskeleton and the cell cortex. Now Toyoshima et al. find that, in HeLa cells, integrin-mediated stimulation of phosphoinositide 3-kinase (PI3K) leading to the production of phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3] at the midsection of the cell cortex in metaphase cells was required for proper spindle orientation. PI(3,4,5)P3 concentration was monitored with a green fluorescent protein fused to the pleckstrin homology domain of Akt (Akt-PH-GFP), and the midsection cortical localization, as well as proper spindle orientation, was lost if PI3K activity was ...
British Library EThOS: Control of cleavage furrow formation during cytokinesis in human cellsBritish Library EThOS: Control of cleavage furrow formation during cytokinesis in human cells
Cytokinesis is the final stage of the cell cycle. It partitions sister genomes and separates the cytoplasm of nascent daughter cells. Cytokinesis is initiated by the formation of a cleavage furrow whose ingression is powered by an actomyosin network known as the contractile ring. Following furrow ingression, the process of cell separation is completed by a membrane scission reaction. For the accurate inheritance of genetic information, it is crucial that furrow formation is initiated at the cell equator between segregating chromosomes and that this occurs after chromatin has cleared the cleavage plane. In animal cells, the mitotic spindle plays a pivotal role in the formation and placement of the cleavage furrow. The coupling of cytokinesis and chromosome segregation to the mitotic spindle ensures that nuclear and cytoplasmic division are tightly coordinated. The spindle midzone, a structure that is formed at anaphase onset between segregating sister genomes, is thought to play an important ...
Bir1p localizes to interpolar microtubules and interact | Open-iBir1p localizes to interpolar microtubules and interact | Open-i
Bir1p localizes to interpolar microtubules and interacts with Ndc10p. (A) Bir1-GFP was imaged in premetaphase cells (top, arrow) and in anaphase cells (bottom,
A novel role for the GTPase-activating protein Bud2 in the spi...A novel role for the GTPase-activating protein Bud2 in the spi...
A novel role for the GTPase-activating protein Bud2 in the spindle position checkpoint.: The spindle position checkpoint (SPC) ensures correct mitotic spindle p
Spindle checkpoint - WikipediaSpindle checkpoint - Wikipedia
During the process of cell division, the spindle checkpoint prevents separation of the duplicated chromosomes until each chromosome is properly attached to the spindle apparatus. In order to preserve the cells identity and proper function, it is necessary to maintain the appropriate number of chromosomes after each cell division. An error in generating daughter cells with fewer or greater number of chromosomes than expected (a situation termed aneuploidy), may lead in best case to cell death, or alternatively it may generate catastrophic phenotypic results. Examples include: In cancer cells, aneuploidy is a frequent event, indicating that these cells present a defect in the machinery involved in chromosome segregation, as well as in the mechanism ensuring that segregation is correctly performed. In humans, Down syndrome appears in children carrying in their cells one extra copy of chromosome 21, as a result of a defect in chromosome segregation during meiosis in one of the progenitors. This ...
DE102014101995A1 - Steering column for a motor vehicle and spindle nut - Google PatentsDE102014101995A1 - Steering column for a motor vehicle and spindle nut - Google Patents
The present invention relates to a steering column (1) for a motor vehicle, comprising a support unit (10, 104) which can be connected to the chassis of the motor vehicle and an actuating unit (10, 104) which is held on this support unit (10, 104) and can be adjusted relative to the support unit (10, 104). 16), which supports a steering spindle (14) for transmitting a steering torque from a steering wheel to a steerable wheel, wherein the actuating unit (16) relative to the support unit (10, 104) via an adjustment (2, 2 ) is adjustable, which is a Threaded rod (26, 26 ) which is in engagement with a female thread (32) having a spindle nut (3) and further comprising a drive motor (20) which acts on an outer toothing (30) of the spindle nut (3) the spindle nut (3) is formed in at least two parts, wherein a toothing part (300) carries the external toothing (30) of the spindle nut (3) and a threaded part (320) the internal thread (32) of the spindle nut (3), and V toothing part (300) and threaded
Spindle epithelial tumour with thymus like differentiation | definition of spindle epithelial tumour with thymus like...Spindle epithelial tumour with thymus like differentiation | definition of spindle epithelial tumour with thymus like...
Looking for online definition of spindle epithelial tumour with thymus like differentiation in the Medical Dictionary? spindle epithelial tumour with thymus like differentiation explanation free. What is spindle epithelial tumour with thymus like differentiation? Meaning of spindle epithelial tumour with thymus like differentiation medical term. What does spindle epithelial tumour with thymus like differentiation mean?
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Microtubules play a prominent role in plant morphogenesis (Kost et al., 1999; Kost and Chua, 2002). Unlike other eukaryote cells, vacuolated and cell wall-confined plant cells follow a specialized mode of cytokinesis, exhibiting four major microtubular arrays at different cell cycle stages with a variety of functions (Goddard et al., 1994). During interphase, a cortical array consisting of parallel microtubules oriented perpendicular to the cell expansion axis assists cellulose deposition (Cyr, 1994) and responds to stimuli (Wymer et al., 1996). At the onset of mitosis, the cortical array is replaced by a densely packed ring of microtubules encircling the nucleus called the preprophase band (PPB), which defines the location of the cell plate formed during cytokinesis (Mineyuki, 1999). Subsequently, the PPB is replaced by a mitotic spindle apparatus consisting of bundles of kinetochore microtubules separating the duplicated chromosomes in daughter cells (Yu et al., 2000). Finally, a phragmoplast ...
Ran at kinetochores | Biochemical Society TransactionsRan at kinetochores | Biochemical Society Transactions
The Ran GTPase controls many cellular functions, including nucleocytoplasmic trafficking, spindle assembly, nuclear assembly and cell-cycle progression. Considerable evidence suggests that diffusible Ran-GTP near mitotic chromatin facilitates the release of critical factors from nuclear transport receptors, thereby promoting organization of mitotic spindles with respect to chromosomes. In addition to this role of soluble Ran-GTP, Ran has two important but less understood roles at mitotic kinetochores. Namely, it is essential for regulation of the spindle assembly checkpoint and for assembly of microtubule fibres that attach kinetochores to spindle poles. Here, I will briefly summarize evidence for these kinetochore-associated functions and mention some of the issues that remain to be addressed regarding them. ...
Social MediaSocial Media
Its with sorrow that we share the news that Emeritus Professor Brian Setchell (BVSc, PhD, ScD) passed away peacefully on July 11. Brian was Professor of Animal Sciences at the Waite Agricultural Research Institute, University of Adelaide, from 1982 until his retirement in 1996. He published The Mammalian Testis, a translation of the original text in Italian by Enrico Sertoli which discusses the cells in the testis now bearing his name. He was involved in translations with H.D. Jocelyn from Latin of Regnier de Graafs two 17C books, on the anatomy of the reproductive systems of men and women, and wrote 76 reviews or chapters in books, 152 articles and 213 abstracts on the physiology, biochemistry and endocrinology of the testis and epididymis, as well as 46 articles on metabolism of the brain and other organs.. He was a passionate musician, a patient accompanist and willing participant in any musical opportunity that came his way. He was a wonderful husband to Marcia, father to Jo, Angus and ...
Researchers unlock secrets of cell division, define role for protein elevated in cancer. ecancer - NewsResearchers unlock secrets of cell division, define role for protein elevated in cancer. ecancer - News
15 Jan 2020. Researchers at Princeton University have successfully recreated a key process involved in cell division in a test tube, uncovering the vital role played by a protein that is elevated in over 25% of all cancers.. The researchers findings, described in a pair of papers published in the journals eLife and Nature Communications, are a key step toward recreating the entire cell division machinery and could lead to new therapies aimed at preventing the growth of cancer cells.. When cells divide, a spindle-like structure composed of thousands of filaments called microtubules attaches to chromosomes and pulls equal numbers of them into each newly forming cell.. Each microtubule is assembled from individual tubulin molecules and, because errors in chromosome segregation can lead to cancer, it is vital that they assemble into microtubules at the right time and place to form a functional spindle apparatus.. Branching microtubule nucleation, in which a new microtubule forms from the side of an ...
Ibd1p, a possible spindle pole body associated protein, regulates nuclear division and bud separation in Saccharomyces...Ibd1p, a possible spindle pole body associated protein, regulates nuclear division and bud separation in Saccharomyces...
TY - JOUR. T1 - Ibd1p, a possible spindle pole body associated protein, regulates nuclear division and bud separation in Saccharomyces cerevisiae. AU - Lee, Jeongkyo. AU - Hwang, Hyung Seo. AU - Kim, Jinmi. AU - Song, Kiwon. PY - 1999/4/1. Y1 - 1999/4/1. N2 - The proper spatial and temporal coordination of mitosis and cytokinesis is essential for maintaining genomic integrity. We describe the identification and characterization of the Saccharomyces cerevisiae IBD1 gene, which encodes a novel protein that regulates the proper nuclear division and bud separation. IBD1 was identified by the limited homology to byr4, a dosage-dependent regulator of cytokinesis in Schizosaccharomyces pombe. IBD1 is not an essential gene, and the knock-out cells show no growth defects except for the reduced mating efficiency [1]. However, upon ectopic expression from an inducible promoter, IBD1 is lethal to the cell and leads to abnormal nuclear division and bud separation. In detail, approximately 90% of the IBD1 ...
Ndc80 targets Bod1 to kinetochores | Open BiologyNdc80 targets Bod1 to kinetochores | Open Biology
To preserve genome integrity, the two sister chromatids of each mitotic chromosome must be distributed equally between daughter cells. Movement of sister chromatids to opposite poles of a dividing cell requires attachment to spindle microtubules of opposing orientation. Errors in the attachment process can lead to chromosome missegregation and aneuploidy (i.e. an aberrant number of chromosomes). Aneuploid karyotypes are the major cause of spontaneous miscarriages in humans [1] and often observed in cancer genomes [2]. A multi-complex protein interface between mitotic chromosomes and the spindle apparatus called the kinetochore is responsible for both the establishment and regulation of the microtubule attachment process [3]. The kinetochore consists of approximately 30 core structural proteins that are arranged into several functional subcomplexes. Structural kinetochore proteins constitute the physical link between chromosomes and spindle microtubules. They also act as a signalling platform by ...
Detailed annotation info for ENST00000235310Detailed annotation info for ENST00000235310
... ; Mitotic spindle assembly checkpoint protein MAD2B (MAD2-like 2) (hREV7). [Source:Uniprot/SWISSPROT;Acc:Q9UI95 ...
Establishment and mitotic characterization of new Drosophila acentriolar cell lines from DSas-4 mutant | Biology OpenEstablishment and mitotic characterization of new Drosophila acentriolar cell lines from DSas-4 mutant | Biology Open
Cell division is an inherent and essential process in living organisms. Different strategies to partition the genetic material and the cytoplasm into daughter cells have emerged during evolution. In prokaryotes, chromosome separation is mostly based on the attachment of DNA to the plasma membrane. A major evolutionary innovation of eukaryotes for chromosome segregation relies on the assembly of a complex bipolar structure, the mitotic spindle, and the linkage of a specialized region of chromosomes, the kinetochore, to spindle microtubules (MTs), allowing the migration of genetic material to spindle poles.. In metazoans the spindle poles are organized around a pair of small organelles, known as centrioles. These structures were probably initially used as basal bodies in order to generate flagellar axonemes allowing cells to have essential functions such as polarity, sensation, and motion. Only later, at the onset of multi-cellular organization, centrioles were recruited to build true centrosomes ...
Saccharomyces cerevisiae MPS2 encodes a membrane protein localized at the spindle pole body and the nuclear envelope -...Saccharomyces cerevisiae MPS2 encodes a membrane protein localized at the spindle pole body and the nuclear envelope -...
Fingerprint Dive into the research topics of Saccharomyces cerevisiae MPS2 encodes a membrane protein localized at the spindle pole body and the nuclear envelope. Together they form a unique fingerprint. ...
Bruce Bowerman (EU) - University of Oregon, USABruce Bowerman (EU) - University of Oregon, USA
ortholog of the Eg5 kinesin that plays an essential role in promoting mitotic spindle bipolarity in most animal phyla. This was surprising, because two large deletion alleles of bmk-1 are homozygous viable, and papers had been published concluding that bmk-1 is not essential in C. elegans (with the only detectable requirement being to modestly decrease the rate of P0 spindle elongation during the first embryonic mitotic cell division). However, our bmk-1(or645ts) allele was 100% embryonic-lethal at 25 degrees C, with monopolar oocyte meiotic spindles, consistent with its known role in promoting spindle bipolarity during mitosis in vertebrates. I convinced myself that the two deletion alleles were not null and we had finally discovered the essential function for bmk-1 in C. elegans. We therefore devoted a great deal of effort toward further characterizing this mutant phenotype. However, one day Rene Medema, at the Netherlands Cancer Institute, emailed me asking if they might use our ...
AneuploidyAneuploidy
ParABS systemParABS system
Hertwig ruleHertwig rule
Actomyosin ringActomyosin ring
Teuthowenia megalopsTeuthowenia megalops
Sperm-associated antigen 5Sperm-associated antigen 5
MitosisMitosis
Cleavage furrowCleavage furrow
OvulationOvulation
KIF15KIF15
Casein kinase 1Casein kinase 1
AKAP9AKAP9
Cell junctionCell junction
TACC3TACC3
MeiosisMeiosis
CytokinesisCytokinesis
William R. BrinkleyWilliam R. Brinkley
ClathrinClathrin
NondisjunctionNondisjunction
ProphaseProphase
Ixcateopan (archaeological site)Ixcateopan (archaeological site)
Cell division orientationCell division orientation
DynactinDynactin
Polo-like kinasePolo-like kinase
CentralspindlinCentralspindlin
ActinActin
Fission (biology)Fission (biology)
User contributions for 96.5.162.193User contributions for 96.5.162.193
Cleavage (embryo)Cleavage (embryo)
Microtubule organizing centerMicrotubule organizing center
PeroxisomePeroxisome
RNA worldRNA world
AutophagyAutophagy
MuscleMuscle
Electronic voice phenomenonElectronic voice phenomenon
Intracellular transportIntracellular transport
Fish jawFish jaw
GlycocalyxGlycocalyx
Fission (biology)Fission (biology)
CDH1 (gene)CDH1 (gene)
MicronucleusMicronucleus
Active zoneActive zone
Aftermath of the Joint Comprehensive Plan of ActionAftermath of the Joint Comprehensive Plan of Action
Cleavage (embryo)Cleavage (embryo)
Medalha Elliott Cresson - Wikipédia, a enciclopédia livreMedalha Elliott Cresson - Wikipédia, a enciclopédia livre
Local anestheticLocal anesthetic
RibosomeRibosome
Cell nucleusCell nucleus
Radial spokeRadial spoke
MicrosomeMicrosome
GingivitisGingivitis
Animal consciousnessAnimal consciousness
endoplasmic reticulumendoplasmic reticulum
EukaryoteEukaryote
ApicomplexaApicomplexa
Muscle relaxantMuscle relaxant
Vocal cordsVocal cords
ProteinoplastProteinoplast
AnatomyOrganismsChemicals and DrugsAnalytical, Diagnostic and Therapeutic Techniques and EquipmentPhenomena and ProcessesInformation Science
Spindle ApparatusNuclear Matrix-Associated ProteinsMitosisMicrotubulesCentrosomeChromosome SegregationTubulinMeiosisMuscle SpindlesGolgi ApparatusCell Cycle ProteinsFluorescent Antibody TechniqueHeLa CellsMolecular Sequence DataAnaphaseKinetochoresMetaphaseKinesinMicrotubule-Associated ProteinsNocodazoleMad2 ProteinsAurora KinasesChromosomesDyneinsTelophaseM Phase Cell Cycle CheckpointsCytokinesisMicroscopy, FluorescenceOocytesProtein-Serine-Threonine KinasesMicrotubule-Organizing CenterSaccharomyces cerevisiae ProteinsMicrotubule ProteinsMutationMicroscopy, ElectronNuclear ProteinsMotor Neurons, GammaCentriolesCell CycleProphaseSaccharomyces cerevisiaePrometaphaseOrganoidsCentromereCell PolarityBirefringenceProtein TransportCdc20 Proteinsran GTP-Binding ProteinAmino Acid SequenceInterphaseXenopus Proteins
Spindle apparatus - WikipediaSpindle apparatus - Wikipedia
Patent US6526011 - Apparatus and method for controlling velocity of spindle motor in optical ... - Google PatentPatent US6526011 - Apparatus and method for controlling velocity of spindle motor in optical ... - Google Patent
Outer domain kinetochore components localize to spindle | Open-iOuter domain kinetochore components localize to spindle | Open-i
Bipolar spindle assembly and failure of chromatin stret | Open-iBipolar spindle assembly and failure of chromatin stret | Open-i
anti-Spindly antibody | GeneTexanti-Spindly antibody | GeneTex
Phase transition of spindle-associated protein regulate spindle apparatus assembly. - PubMed - NCBIPhase transition of spindle-associated protein regulate spindle apparatus assembly. - PubMed - NCBI
Specific attachment of nuclear-mitotic apparatus protein to metaphase chromosomes and mitotic spindle poles: possible function...Specific attachment of nuclear-mitotic apparatus protein to metaphase chromosomes and mitotic spindle poles: possible function...
Accurate measurement of poleward microtubule flux in the spindle of Drosophila S2 cellsAccurate measurement of poleward microtubule flux in the spindle of Drosophila S2 cells
Spindle ApparatusSpindle Apparatus
A Novel Role of the Budding Yeast Separin Esp1 in Anaphase Spindle Elongation | JCBA Novel Role of the Budding Yeast Separin Esp1 in Anaphase Spindle Elongation | JCB
A case of oculomotor nerve palsy associated with antimitotic spindle a | OPTHA case of oculomotor nerve palsy associated with antimitotic spindle a | OPTH
Interaction of CK1δ with γTuSC ensures proper microtubule assembly and spindle positioning. - NextBio articleInteraction of CK1δ with γTuSC ensures proper microtubule assembly and spindle positioning. - NextBio article
Absence of Centrioles in the First and Second Meiotic Spindles of Mouse Oocytes | Journal of Cell ScienceAbsence of Centrioles in the First and Second Meiotic Spindles of Mouse Oocytes | Journal of Cell Science
User contributions for 96.5.162.193 - WikipediaUser contributions for 96.5.162.193 - Wikipedia
Traction fibre: toward a tensegral model of the spindle. - Semantic ScholarTraction fibre: toward a "tensegral" model of the spindle. - Semantic Scholar
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Microtubule organization within mitotic spindles revealed by serial block face scanning electron microscopy and image analysis ...Microtubule organization within mitotic spindles revealed by serial block face scanning electron microscopy and image analysis ...
Aneuploidy - WikipediaAneuploidy - Wikipedia
A Novel Role of the Budding Yeast Separin Esp1 in Anaphase Spindle Elongation | Journal of Cell Biology | Rockefeller...A Novel Role of the Budding Yeast Separin Esp1 in Anaphase Spindle Elongation | Journal of Cell Biology | Rockefeller...
NHANES 2003-2004: Autoantibodies - Immunofluorescence & Immunoprecipitation Analyses (Surplus) Data Documentation,...NHANES 2003-2004: Autoantibodies - Immunofluorescence & Immunoprecipitation Analyses (Surplus) Data Documentation,...
IP 505: Bitumen and bituminous binders - Determination of viscosity of bitumen using a rotating spindle apparatus | EI ...IP 505: Bitumen and bituminous binders - Determination of viscosity of bitumen using a rotating spindle apparatus | EI ...
HOW DOES E. COLI SEGREGATE ITS SISTERS WITHOUT A SPINDLE? [KLECKNER LAB] - Harvard University - Department of Molecular &...HOW DOES E. COLI SEGREGATE ITS SISTERS WITHOUT A SPINDLE? [KLECKNER LAB] - Harvard University - Department of Molecular &...
Genetic Basis Of LifeGenetic Basis Of Life
The novel BTB-kelch protein, KBTBD8, is located in the Golgi apparatus and translocates to the spindle apparatus during mitosis...The novel BTB-kelch protein, KBTBD8, is located in the Golgi apparatus and translocates to the spindle apparatus during mitosis...
subito Encodes a Kinesin-like Protein Required for Meiotic Spindle Pole Formation in Drosophila melanogaster | Geneticssubito Encodes a Kinesin-like Protein Required for Meiotic Spindle Pole Formation in Drosophila melanogaster | Genetics
Meiosis II | Protocol (Translated to Spanish)Meiosis II | Protocol (Translated to Spanish)
Abstract 3460: TBK1 regulates mitotic progression by modulating spindle assembly checkpoint in cancer cells | Cancer ResearchAbstract 3460: TBK1 regulates mitotic progression by modulating spindle assembly checkpoint in cancer cells | Cancer Research
Recombinant Human CLASP1 protein (ab161605) | AbcamRecombinant Human CLASP1 protein (ab161605) | Abcam
Human TPX2 is required for targeting Aurora-A kinase to the spindle | JCBHuman TPX2 is required for targeting Aurora-A kinase to the spindle | JCB
Patent US4485337 - Servo data driven motor speed control - Google PatentsPatent US4485337 - Servo data driven motor speed control - Google Patents
Phase separation at the synapse | Nature NeurosciencePhase separation at the synapse | Nature Neuroscience
Graphene Multielectrode Arrays as a Versatile Tool for Extracellular Measurements.Graphene Multielectrode Arrays as a Versatile Tool for Extracellular Measurements.
MAD1L1 | Cancer Genetics WebMAD1L1 | Cancer Genetics Web
AnatomyOrganismsChemicals and DrugsAnalytical, Diagnostic and Therapeutic Techniques and EquipmentPhenomena and ProcessesInformation Science
Spindle ApparatusNuclear Matrix-Associated ProteinsMitosisMicrotubulesCentrosomeChromosome SegregationTubulinMeiosisMuscle SpindlesGolgi ApparatusCell Cycle ProteinsFluorescent Antibody TechniqueHeLa CellsMolecular Sequence DataAnaphaseKinetochoresMetaphaseKinesinMicrotubule-Associated ProteinsNocodazoleMad2 ProteinsAurora KinasesChromosomesDyneinsTelophaseM Phase Cell Cycle CheckpointsCytokinesisMicroscopy, FluorescenceOocytesProtein-Serine-Threonine KinasesMicrotubule-Organizing CenterSaccharomyces cerevisiae ProteinsMicrotubule ProteinsMutationMicroscopy, ElectronNuclear ProteinsMotor Neurons, GammaCentriolesCell CycleProphaseSaccharomyces cerevisiaePrometaphaseOrganoidsCentromereCell PolarityBirefringenceProtein TransportCdc20 Proteinsran GTP-Binding ProteinAmino Acid SequenceInterphaseXenopus Proteins
MitosisChromosomesMeioticProteinRole in mitotic spindleCentrosomesKinetochoresProteinsKinetochoreDrosophilaBipolar spindleOocytesAssemblyAnastralMidzoneAntibodiesSister chromatidsMeiosisAnaphaseFibresOocytesTubulinProphaseAstersCellsCentrosomeDepletionMicroscopyMicrotubules in the spindleCentriolesChromatinMeiotic spindle assemblyXenopusMonopolar spindleFormationOrientationMuscle spindlesOppositeAntibodyAstral microtubules
Mitosis5
Chromosomes5
Meiotic2
Protein6
Role in mitotic spindle1
Centrosomes3
Kinetochores5
Proteins2
Kinetochore2
Drosophila3
Bipolar spindle1
Oocytes1
Assembly4
Anastral1
Midzone1
Antibodies2
Sister chromatids1
Meiosis3
Anaphase22
Fibres5
Oocytes10
Tubulin4
Prophase3
Asters2
Cells24
Centrosome3
Depletion3
  • B-E. Representative images ( B ) show that xBuGZ depletion reduced astral MT length, bipolar spindle formation and length, which were all rescued by His-xBuGZ. (nih.gov)
  • F-H. xBuGZ depletion caused multiple sperm spindle defects ( F ), which was rescued by His-xBuGZ ( G , H ). ~500 ( G ) and ~50 ( H ) structures were analyzed in each experiment and condition. (nih.gov)
  • Depletion of TBK1 was shown to trigger defects in spindle apparatus and prevents mitotic progression (Pillai et al. (aacrjournals.org)
Microscopy1
Microtubules in the spindle2
Centrioles2
Chromatin3
  • Shown are maximum intensity projections of the chromatin masses of oocyte meiotic spindles. (nih.gov)
  • The duplicated chromatin condenses, spindle apparatus forms, nucleoli and nuclear membrane disappears, homologous chromosomes intertwine (synapsis) resulting in a tetrad of 4 chromatids which cross over. (studystack.com)
  • The chromatin is stained with a blue fluorescent probe (DAPI), while the microtubule network (mitotic spindle) is stained green (Alexa Fluor 488) and cellular mitochondria are stained with a red dye (MitoTracker Red CMXRos). (fsu.edu)
Meiotic spindle assembly1
  • An excellent study published in the medical journal "Human Reproduction" in October of 1996 investigated the influence of maternal age on meiotic spindle assembly in human eggs. (advancedfertility.com)
Xenopus1
Monopolar spindle1
  • A tetraploid intermediate may be produced as the end-result of the monopolar spindle mechanism. (wikipedia.org)
Formation8
Orientation1
  • We illustrate how Pitx2 activity directs asymmetrical gonad morphogenesis by controlling mitotic spindle orientation of the developing gonad cortex and how, by modulating cyclinD1 expression during asymmetric ovarian development, Pitx2 appears to control gonad organ size. (biomedsearch.com)
Muscle spindles3
  • Neural activity from muscle spindles in the multifidus and longissimus muscles were recorded from L6 dorsal rootlets in 16 anesthetized cats. (chiro.org)
  • This animal study showed that contact site for an HVLA-SM can have a significant effect on the magnitude of sensory input arising from muscle spindles in the back. (chiro.org)
  • muscle spindles function and structure,What You are Looking For? (openraam.eu)
Opposite1
Antibody1
Astral microtubules1