TY - JOUR. T1 - Mitotic centromere-associated kinesin is a novel marker for prognosis and lymph node metastasis in colorectal cancer. AU - Ishikawa, K.. AU - Kamohara, Y.. AU - Tanaka, F.. AU - Haraguchi, N.. AU - Mimori, K.. AU - Inoue, H.. AU - Mori, M.. N1 - Funding Information: We thank Dr Y Nakamura, Ms T Shimooka, Ms K Ogata, Ms M Kasagi and Ms Y Nakagawa for their technical assistance and advice. This work was supported in part by the following grants and foundations: CREST, Japan Science and Technology Agency; Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research, grants 17109013, 17591411, 17591413, 18390367, 18590333, 18659384, 18790964, 19890336 and 19591509; The Ministry of Education, Culture, Sports, Science and Technology Grant-in-Aid for Scientific Research on Priority Areas, Grant 18015039; Third Term Comprehensive Ten-Year Strategy for Cancer Control, Grant 16271201.. PY - 2008/6/3. Y1 - 2008/6/3. N2 - Mitotic centromere-associated kinesin (MCAK) is a ...

1. Howard J. The movement of kinesin along microtubules. Annu Rev Physiol. 1996;58:703-729 2. Hirokawa N. Kinesin and dynein superfamily proteins and the mechanism of organelle transport. Science. 1998;279:519-526 3. Vale RD. The molecular motor toolbox for intracellular transport. Cell. 2003;112:467-480 4. Cross RA. The kinetic mechanism of kinesin. Trends Biochem Sci. 2004;29:301-309 5. Asbury CL. Kinesin: worlds tiniest biped. Curr Opin Cell Biol. 2005;17:89-97 6. Lawrence CJ, Dawe RK, Christie KR. et al. A standardized kinesin nomenclature. J Cell Biol. 2004;167:19-22 7. Howard J, Hudspeth AJ, Vale RD. Movement of microtubules by single kinesin molecules. Nature. 1989;342:154-158 8. Block SM, Goldstein LS, Schnapp BJ. Bead movement by single kinesin molecules studied with optical tweezers. Nature. 1990;348:348-352 9. Svoboda K, Block SM. Force and velocity measured for single kinesin molecules. Cell. 1994;77:773-784 10. Meyhöfer E, Howard J. The force generated by a single kinesin molecule ...

Dynein and kinesin motor proteins transport cellular cargoes toward opposite ends of microtubule tracks. In neurons, microtubules are abundantly decorated with microtubule-associated proteins (MAPs) such as tau. Motor proteins thus encounter MAPs frequently along their path. To determine the effects of tau on dynein and kinesin motility, we conducted single-molecule studies of motor proteins moving along tau-decorated microtubules. Dynein tended to reverse direction, whereas kinesin tended to detach at patches of bound tau. Kinesin was inhibited at about a tenth of the tau concentration that inhibited dynein, and the microtubule-binding domain of tau was sufficient to inhibit motor activity. The differential modulation of dynein and kinesin motility suggests that MAPs can spatially regulate the balance of microtubule-dependent axonal transport.. ...

Kinesin motor protein, molecular model. Kinesin motor proteins transport vesicles containing intracellular cargo around the cell along microtubules. - Stock Image F009/6428

Kinesin was previously immunolocalized to mitotic apparatuses (MAs) of early sea urchin blastomeres (Scholey, J.M., M.E. Porter, P.M. Grissom, and J.R. McIntosh. 1985. Nature [Lond.]. 318:483-486). Here we report evidence that this MA-associated motor protein is a conventional membrane-bound kinesin, rather than a kinesin-like protein. Our evidence includes the observation that the deduced amino acid sequence of this sea urchin kinesin heavy chain is characteristic of a conventional kinesin. In addition, immunolocalizations using antibodies that distinguish kinesin from kinesin-like proteins confirm that conventional kinesin is concentrated in MAs. Finally, our immunocytochemical data further suggest that conventional kinesin is associated with membranes which accumulate in MAs and interphase asters of early sea urchin embryos, and with vesicles that are distributed in the perinuclear region of coelomocytes. Thus kinesin may function as a microtubule-based vesicle motor in some MAs, as well as ...

Kinesin Family Member C1 (KIFC1) Regulated by Centrosome Protein E (CENPE) Promotes Proliferation, Migration, and Epithelial-Mesenchymal Transition of Ovarian Cancer - Related articles #927869

Ready-to-use Adenovirus expressing shRNA for silencing of Human KIF3A (kinesin family member 3A). Available with optional GFP reporter or cell-specific promoter.

The kinesin tree was built from a sequence alignment of 144 kinesin motor domains from 31 species using the heuristic search method of PAUP v. 4.0b4a ( Swofford, 1998), a maximum parsimony program, and random stepwise addition and tree-bisection-reconnection (TBR) branch swapping. The tree is one of six optimal trees that were found in ,530 tree-building trials and is arbitrarily rooted, using ScSmy1 as an outgroup protein. ScSmy1 is not known to be the ancestral kinesin but is a highly divergent kinesin protein. The numbers adjacent to nodes are the percentages of 950 bootstrap trials, performed by the heuristic method of PAUP and simple stepwise addition, in which the groups to the right were found. Horizontal branch lengths are proportional to the number of amino acid changes needed to explain the differences in protein sequences, as indicated by the scale. The tree has an overall length of 14,336.. Two kinesin subfamilies (KRP85/95, Unc104/KIF1) had bootstrap values of ,90% by maximum ...

Kinesin is a processive motor that takes 8.3-nm center-of-mass steps along microtubules for each adenosine triphosphate hydrolyzed. Whether kinesin moves by a ``hand-over-hand or an ``inchworm model has been controversial. We have labeled a single head of the kinesin dimer with a Cy3 fluorophore and localized the position of the dye to within 2 nm before and after a step. We observed that single kinesin heads take steps of 17.3 +/- 3.3 nm. A kinetic analysis of the dwell times between steps shows that the 17-nm steps alternate with 0-nm steps. These results strongly support a hand-over-hand mechanism, and not an inchworm mechanism. In addition, our results suggest that kinesin is bound by both heads to the microtubule while it waits for adenosine triphosphate in between steps. |P /|

The motor protein kinesin couples a temporally periodic chemical cycle (the hydrolysis of ATP) to a spatially periodic mechanical cycle (movement along a microtubule). To distinguish between different models of such chemical-to-mechanical coupling, we measured the speed of movement of conventional kinesin along microtubules in in vitro motility assays over a wide range of substrate (ATP) and product (ADP and inorganic phosphate) concentrations. In the presence and absence of products, the dependence of speed on [ATP] was well described by the Michaelis-Menten equation. In the absence of products, the K(M) (the [ATP] required for half-maximal speed) was 28 +/- 1 microM, and the maximum speed was 904 nm/s. P(i) behaved as a competitive inhibitor with K(I) = 9 +/- 1 mM. ADP behaved approximately as a competitive inhibitor with K(I) = 35 +/- 2 microM. The data were compared to four-state kinetic models in which changes in nucleotide state are coupled to chemical and/or mechanical changes. We found ...

Lagging chromosomes during anaphase are an easily assayed and therefore commonly reported mitotic defect. However, in most cases, the mechanisms that give rise to lagging chromosomes are unknown. Lagging chromosomes can be caused by asbestos fibers (Hersterberg and Barrett, 1985), elevated ras p21 expression (Hagag et al., 1990), carcinogens such as diethylstilbestrol (Schiffmann and De Boni, 1991), and inherited genetic conditions such as Roberts syndrome (Jabs et al., 1991). Chromosomes, chromatids, and chromosome fragments that do not segregate properly often end up spatially separated from the bulk of the chromosomes and will reform a separate nuclear envelope after mitosis is completed. This results in a cell containing micronuclei. Sometimes these cells are described as multinucleate. Severe chromosome segregation defects will in turn inhibit cytokinesis giving rise to truly multinucleate cells (Schultz and Onfelt, 1994). The mechanism by which these diverse agents disrupt anaphase ...

Sigma-Aldrich offers abstracts and full-text articles by [Mourad Sanhaji, Andreas Ritter, Hannah R Belsham, Claire T Friel, Susanne Roth, Frank Louwen, Juping Yuan].

We have isolated a human homolog of Xenopus Eg5, a kinesin-related motor protein implicated in the assembly and dynamics of the mitotic spindle. We report that microinjection of antibodies against human Eg5 (HsEg5) blocks centrosome migration and causes HeLa cells to arrest in mitosis with monoastra …

We have isolated a human homolog of Xenopus Eg5, a kinesin-related motor protein implicated in the assembly and dynamics of the mitotic spindle. We report that microinjection of antibodies against human Eg5 (HsEg5) blocks centrosome migration and causes HeLa cells to arrest in mitosis with monoastra …

TY - JOUR. T1 - Unique function of Kinesin Kif5A in localization of mitochondria in axons. AU - Campbell, Philip D.. AU - Shen, Kimberle. AU - Sapio, Matthew R.. AU - Glenn, Thomas D.. AU - Talbot, William S.. AU - Marlow, Florence L.. PY - 2014/10/29. Y1 - 2014/10/29. N2 - Mutations in Kinesin proteins (Kifs) are linked to various neurological diseases, but the specific and redundant functions of the vertebrate Kifs are incompletely understood. For example, Kif5A, but not other Kinesin-1 heavy-chain family members, is implicated in Charcot-Marie-Tooth disease (CMT) and Hereditary Spastic Paraplegia (HSP), but the mechanism of its involvement in the progressive axonal degeneration characteristic of these diseases is not well understood. We report that zebrafish kif5Aa mutants exhibit hyperexcitability, peripheral polyneuropathy, and axonal degeneration reminiscent of CMT and HSP. Strikingly, although kif5 genes are thought to act largely redundantly in other contexts, and zebrafish peripheral ...

An additional genetic locus in Caenorhabditis elegans, unc-116, was identified in a screen for mutations resulting in defective locomotion. unc-116 was cloned by use of a transposon insertion mutant and the physical and genetic map of the genome. The cDNA sequence predicts an 815-amino acid protein. Based upon sequence comparison and secondary structure predictions, unc-116 encodes all three domains of the kinesin heavy chain: the motor, stalk, and tail. While the motor and tail domains have a high degree of identity to the equivalent domains of cloned kinesin heavy chains, the rodII domain of the stalk is significantly shorter than those previously reported and is not predicted to form a coiled-coil alpha-helix. Analysis of mutational defects in two C. elegans genes encoding anterograde motor molecules, unc-116 and unc-104, should provide insight into the in vivo functions of these members of the kinesin heavy chain superfamily.. ...

The protein encoded by this gene is a member of kinesin-like protein family. This family of proteins are microtubule-dependent molecular motors that transport organelles within cells and move chromosomes during cell division. The C-terminal half of this protein has been shown to bind DNA. Studies with the Xenopus homolog suggests its essential role in metaphase chromosome alignment and maintenance.

BioAssay record AID 242686 submitted by ChEMBL: In vitro inhibitory concentration towards kinesin spindle protein activity of ATP hydrolysis in the presence of microtubules measured by ATPase assay (n=3).

Author Summary Proteins belonging to the kinesin superfamily are responsible for vesicle or organelle transport, spindle morphogenesis, and chromosome sorting during cell division. Interestingly, while most proteins in kinesin superfamily that share the common catalytic motor head domain have plus-end directionality along microtubules, kinesin-14 (Ncd) exhibits minus-end directionality. Despite the several circumstantial evidences on the determining factors for the motor directionality in the last decade, a comprehensive understanding of the mechanism governing the Ncd minus-end directionality is still missing. Our studies provide a clear explanation for this minus-end directionality and the associated mechanochemical cycle. Here, we modeled an Ncd motor by employing structural details available in the literature to simulate its conformational dynamics. Simulations using our structure-based model of Ncd assert that the dynamics due to a simple rearrangement of structural elements, peripheral to the

View mouse Kif26b Chr1:178356690-178766765 with: phenotypes, sequences, polymorphisms, proteins, references, function, expression

TY - JOUR. T1 - Delayed start-up of kinesin-driven microtubule gliding following inhibition by adenosine 5′-[β,γ-imido]triphosphate. AU - Schnapp, Bruch J.. AU - Crise, Bruce. AU - Sheetz, Michael. AU - Reese, Thomas S.. AU - Khan, Shahid. PY - 1990/1/1. Y1 - 1990/1/1. N2 - Kinesin is a microtubule-activated ATPase that moves objects toward the plus end of microtubules and makes microtubules glide along a glass surface. Here we investigate a remarkable effect of the nonhydrolyzable analogue of ATP, adenosine 5′-[β,γ-imido]triphosphate (p[NH]ppA), on kinesin-driven microtubule gliding. Microtubule gliding that has been blocked by rapid replacement of ATP with p[NH]ppA requires 1-2 min of exposure to ATP before microtubule gliding resumes. This latency is not shortened by prolonged washing of p[NH]ppA-blocked microtubules in nucleotide-free buffer for up to 15 min, suggesting that ATP binding to a second nucleotide binding site on kinesin triggers the release of bound p[NH]ppA. To test ...

There are treatments for schizophrenia, but they have side effects and unfortunately there is still no effective drug for patients to take that we can explain biochemically why it works, explained Hirokawa.. Genetic studies of people diagnosed with schizophrenia have found possible links between the disease and variations in the kinesin family 3b (kif3b) gene as well as another gene involved in the bodys internal synthesis of betaine.. Hirokawa and his lab members have categorized all 45 members of the kinesin superfamily of genes in mammals, most of which encode motor proteins that move materials throughout the cell. Normally, the KIF3B protein links together with another kinesin superfamily protein and transports cargo throughout a neuron by traveling up and down the cells skeleton.. Mice used in the recent research had only one functional copy of the kif3b gene and are often used as an animal model of schizophrenia. These mice avoid social interactions and show the same weak response as ...

In the study of motor proteins, the molecular mechanism of mechanochemical coupling, as well as the cellular role of these proteins, is an important issue. To assess these questions we introduced cDNA of wild-type and site-directed mutant kinesin heavy chains into fibroblasts, and analyzed the behavior of the recombinant proteins and the mechanisms involved in organelle transports. Overexpression of wild-type kinesin significantly promoted elongation of cellular processes. Wild-type kinesin accumulated at the tips of the long processes, whereas the kinesin mutants, which contained either a T93N- or T93I mutation in the ATP-binding motif, tightly bound to microtubules in the center of the cells. These mutant kinesins could bind to microtubules in vitro, but could not dissociate from them even in the presence of ATP, and did not support microtubule motility in vitro, thereby indicating rigor-type mutations. Retrograde transport from the Golgi apparatus to the endoplasmic reticulum, as well as ...

1. HirokawaN. TakemuraR. 2005 Molecular motors and mechanisms of directional transport in neurons. Nat Rev Neurosci 6 201 214. 2. GoldsteinAY. WangX. SchwarzTL. 2008 Axonal transport and the delivery of pre-synaptic components. Curr Opin Neurobiol 18 495 503. 3. HallDH. HedgecockEM. 1991 Kinesin-related gene unc-104 is required for axonal transport of synaptic vesicles in C. elegans. Cell 65 837 847. 4. Pack-ChungE. KurshanPT. DickmanDK. SchwarzTL. 2007 A Drosophila kinesin required for synaptic bouton formation and synaptic vesicle transport. Nat Neurosci 10 980 989. 5. BarkusRV. KlyachkoO. HoriuchiD. DicksonBJ. SaxtonWM. 2008 Identification of an axonal kinesin-3 motor for fast anterograde vesicle transport that facilitates retrograde transport of neuropeptides. Mol Biol Cell 19 274 283. 6. OkadaY. YamazakiH. Sekine-AizawaY. HirokawaN. 1995 The neuron-specific kinesin superfamily protein KIF1A is a unique monomeric motor for anterograde axonal transport of synaptic vesicle precursors. Cell 81 ...

Binding of extracellular netrin-1 to its receptors, deleted in colorectal cancer (DCC) and uncoordinated gene 5H2 (UNC5H2), inhibits apoptosis mediated by these receptors. A neuron-specific kinesin motor protein, KIF1A, has been shown to participate in netrin-1 secretion. This study aimed to identify the roles of netrin-1 and KIF1A in secondary brain injury after intracerebral hemorrhage (ICH) and the potential mechanisms. An autologous blood ICH model was established in adult male Sprague-Dawley rats, and cultured neurons were exposed to OxyHb to mimic ICH conditions in vitro. Mouse recombinant netrin-1, expression vectors encoding KIF1A, and KIF1A-specific siRNAs were administered intracerebroventricularly. After ICH, protein levels of netrin-1, DCC, and UNC5H2 increased, while protein levels of KIF1A decreased. Levels of UNC5H2 and DCC bound to netrin-1 increased after ICH but were significantly lower than the increase in total amount of protein. Administration of recombinant netrin-1 attenuated

In 2012, Li et al. [26] conducted a GWAS that included two independent Han cohorts at the genome-wide discovery stage, and they covered 480 HBV-positive HCC patients and 484 chronic HBV carriers from central China and 1,058 cases and 981 controls from southern China. These authors assessed the previously reported HCC-susceptible SNP rs17401966; however, the merged results for the two groups showed that the rs17401966 G allele did not reduce the risk of HCC (OR=0.90; 95% CI: 0.80-1.02). In 2013, Jiang et al. [27] conducted another GWAS with 1161 cases and 1,353 controls from Qidong at the genome-wide discovery stage, although the findings were not confirmed (OR=0.98; 95% CI: 0.87-1.11). Subsequent studies by other scholars also failed to achieve consistent results [16-19]. Because the role of the same gene can vary among different populations, among the same group and among with the same tumor, a single study may not provide enough samples for a correlation analysis or sufficient statistical ...

MKlp2 is a kinesin-like motor protein of the central mitotic spindle required for completion of cytokinesis. Papillomavirus E2 is a sequence specific DNA binding protein that regulates viral transcription and replication and is responsible for partitioning viral episomes into daughter cells during cell division. We demonstrate that MKlp2 specifically associates with the E2 protein during mitosis. Using chromatin immunoprecipitation, we show viral genomes are in complex with MKlp2 only within this stage of cell cycle. By immunofluorescence, a subpopulation of papillomavirus E2 colocalizes with MKlp2 in the midbody/midplate during late mitosis. We conclude that during specific stages of mitosis, the papillomavirus E2 protein binds to MKlp2, and infer that association with this motor protein ensures viral genome partitioning during cytokinesis.

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In general, this assay seemed to have a very very low reaction, really really low. When the redo calibration is subtracted from the later measurements, the absorbances are about 0.008, which relates to about 1-5 uM Pi. At 24 hours, the absorbance is about 0.027, which relates to a Pi concentration of about 12 uM. So it is still pretty low. But at lest it is active! Also, I have noticed that malachite green is very quick, and changes very quickly even at 10 minutes. By measuring even 30 seconds too late, absorbances seem to be about 0.01 larger. So it is very possible that much of the data was taken slightly later than intended and thus artificially high, or slightly earlier and artificially low. So in the future I need to be hyper-vigilant about getting them in on time, or to measure a sample and see where the malachite green begins to decelerate and shot for that developing time. When I did this assay previously, I saw results directly from kinesin activity. I used about 5x more tubulin than ...

The inability to faithfully segregate chromosomes in mitosis results in chromosome instability, a hallmark of solid tumors. Disruption of microtubule dynamics contributes highly to mitotic chromosome instability. The kinesin-13 family is critical in the regulation of microtubule dynamics and the best characterized member of the family, the mitotic centromere-associated kinesin (MCAK), has recently been attracting enormous attention. MCAK regulates microtubule dynamics as a potent depolymerizer of microtubules by removing tubulin subunits from the polymer end. This depolymerizing activity plays pivotal roles in spindle formation, in correcting erroneous attachments of microtubule-kinetochore and in chromosome movement. Thus, the accurate regulation of MCAK is important for ensuring the faithful segregation of chromosomes in mitosis and for safeguarding chromosome stability. In this review we summarize recent data concerning the regulation of MCAK by mitotic kinases, Aurora A/B, Polo-like kinase 1 ...

klp-10 encodes a kinesin-like motor protein that displays similarity to diverse types of kinesin motor domains such as those found in C. elegans OSM-3, the vertebrate CHO1/MKLP proteins, and Saccharomyces cerevisiae Kip3; KLP-10 is required for embryogensis, may play a role in meiosis, and has been implicated in chromosome segregation and cell cycle progression ...

To see if the motor can be arrested in a particular configuration by the help of a ligand, so that it becomes dysfunctional and inhibits cell division leading to apoptosis.

TY - JOUR. T1 - The kinesin-5 tail domain directly modulates the mechanochemical cycle of the motor domain for anti-parallel microtubule sliding. AU - Bodrug, Tatyana. AU - Wilson-Kubalek, Elizabeth. AU - Nithianantham, Stanley. AU - Thompson, Alex F.. AU - Alfieri, April. AU - Gaska, Ignas. AU - Major, Jennifer. AU - Debs, Garret. AU - Inagaki, Sayaka. AU - Gutierrez, Pedro. AU - Gheber, Larisa. AU - McKenney, Richard. AU - Sindelar, Charles. AU - Milligan, Ronald. AU - Stumpff, Jason. AU - Rosenfeld, Steven. AU - Forth, Scott T.. AU - Al-Bassam, Jawdat. PY - 2020/1. Y1 - 2020/1. N2 - Kinesin-5 motors organize mitotic spindles by sliding apart microtubules. They are homotetramers with dimeric motor and tail domains at both ends of a bipolar minifilament. Here, we describe a regulatory mechanism involving direct binding between tail and motor domains and its fundamental role in microtubule sliding. Kinesin-5 tails decrease microtubule-stimulated ATP-hydrolysis by specifically engaging motor ...

TY - JOUR. T1 - Xenopus Staufen is a component of a ribonucleoprotein complex containing Vg1 RNA and kinesin. AU - Yoon, Young J.. AU - Mowry, Kimberly L.. PY - 2004/7. Y1 - 2004/7. N2 - RNA localization is a key mechanism for generating cell and developmental polarity in a wide variety of organisms. We have performed studies to investigate a role for the Xenopus homolog of the double-stranded RNA-binding protein, Staufen, in RNA localization during oogenesis. We have found that Xenopus Staufen (XStau) is present in a ribonucleoprotein complex, and associates with both a kinesin motor protein and vegetally localized RNAs Vg1 and VegT. A functional role for XStau was revealed through expression of a dominant-negative version that blocks localization of Vg1 RNA in vivo. Our results suggest a central role for XStau in RNA localization in Xenopus oocytes, and provide evidence that Staufen is a conserved link between specific mRNAs and the RNA localization machinery.. AB - RNA localization is a key ...

Cell division is all about precise separation of sister chromatids to the daughter cells. In fact, cells have a fail-safe mechanism known as the mitotic checkpoint through which the cell division process is only allowed to proceed if every chromosome is attached to the microtubules of the mitotic spindle. Malfunction of this process is thought to contribute to chromosome instability in cancer cells. Some controversy has surrounded the question of whether the checkpoint mechanism actually senses attachment to microtubules per se or the tension that results from it. Mao et al. provide new experiments that support the former model. BubR1 is a protein kinase that is active at unattached kinetichores and contributes to the signal that stops progression of anaphase. The centromere-associated kinesin family member CENP-E binds to and stimulates BubR1, and the motor domain of CENP-E binds microtubules. Mao et al. show in Xenopus egg extracts or transfected mammalian cells that a form of CENP-E that ...

Kinesin-8s are plus-end-directed motors that negatively regulate microtubule (MT) length. Well-characterized members of this subfamily (Kip3, Kif18A) exhibit two important properties: (i) They are ultraprocessive, a feature enabled by a second MT-binding site that tethers the motors to a MT track, and (ii) they dissociate infrequently from the plus end. Together, these characteristics combined with their plus-end motility cause Kip3 and Kif18A to enrich preferentially at the plus ends of long MTs, promoting MT catastrophes or pausing. Kif18B, an understudied human kinesin-8, also limits MT growth during mitosis. In contrast to Kif18A and Kip3, localization of Kif18B to plus ends relies on binding to the plus-end tracking protein EB1, making the relationship between its potential plus-end-directed motility and plus-end accumulation unclear. Using single-molecule assays, we show that Kif18B is only modestly processive and that the motor switches frequently between directed and diffusive modes of ...

Plus end-directed microtubule-dependent motor required for normal brain development. May regulate microtubule dynamics during axonal growth. Required for normal progression through mitosis. Required for normal congress of chromosomes at the metaphase plate. Required for normal spindle dynamics during mitosis. Promotes spindle turnover. Implicated in formation of bipolar mitotic spindles. Has microtubule depolymerization activity.

Tulin A, McClerklin S, Huang Y and Dixit R (2012). Single-molecule analysis of the microtubule crosslinking protein MAP65-1 reveals a molecular mechanism for contact-angle-dependent microtubule bundling. Biophysical Journal, 102: 802-809.. Eren EC, Gautam N and Dixit R (2012). Computer simulation and mathematical models of the noncentrosomal plant cortical microtubule cytoskeleton. Cytoskeleton, 69: 144-154.. Zhu C and Dixit R (2012). Functions of the Arabidopsis kinesin superfamily of microtubule-based motor proteins. Protoplasma, 249: 887-899.. Dixit R (2012). Putting a bifunctional motor to work: insights into the role of plant KCH kinesins. New Phytologist, 193: 543-545.. Zhu C and Dixit R (2011). Single molecule analysis of the Arabidopsis FRA1 kinesin shows that it is a functional motor protein with unusually high processivity. Molecular Plant, 4: 879-885... Sun F, Zhu C, Dixit R and Cavalli V (2011). Sunday Driver /JIP3 binds kinesin heavy chain directly and enhances its motility. EMBO J, ...

ENCODES a protein that exhibits kinesin binding; microtubule binding; INVOLVED IN axo-dendritic transport; ASSOCIATED WITH xeroderma pigmentosum (ortholog); FOUND IN ciliary rootlet; cytoplasm; motile cilium; INTERACTS WITH 4-hydroxyphenyl retinamide; Aroclor 1254; choline

4AQV: Model of human kinesin-5 motor domain (3HQD) and mammalian tubulin heterodimer (1JFF) docked into the 9.7-angstrom cryo-EM map of microtubule-bound kinesin-5 motor domain in the AMPPPNP state.

Motor proteins display widely different stepping patterns as they move on microtubule tracks, from the deterministic linear or helical motion performed by the protein kinesin to the uncoordinated random steps made by dynein. How these different strategies produce an efficient navigation system needed to ensure correct cellular functioning is still unclear. Here, we show by numerical simulations that deterministic and random motor steps yield different outcomes when random obstacles decorate the microtubule tracks: kinesin moves faster on clean tracks but its motion is strongly hindered on decorated tracks, while dynein is slower on clean tracks but more efficient in avoiding obstacles. Further simulations indicate that dyneins advantage on decorated tracks is due to its ability to step backwards. Our results explain how different navigation strategies are employed by the cell to optimize motor driven cargo transport ...

A superfamily of proteins found in cells that contain microtubules. One function of the kinesin motor protein is to move vesicles and particles laterally along these tubules toward their distal ends. Kinetochores also contain specific kinesins that drive each kinetochore along the spindle microtubules toward the poles. ...

Our goal is to understand how kinesin motors function in live cells, that is, in the presence of relevant cargo and regulatory proteins and under the physical and physiological constraints of the cytoplasm. We use a variety of methods, from biophysical to cell biological, to investigate kinesin motors from the single molecule to the cellular level. Relevant questions include: How do kinesin motors bind their cargoes and become activated for transport? How do kinesin motors navigate the complex microtubule network in cells? How do multiple motors on the surface of a cargo coordinate their activities ...

Our goal is to understand how kinesin motors function in live cells, that is, in the presence of relevant cargo and regulatory proteins and under the physical and physiological constraints of the cytoplasm. We use a variety of methods, from biophysical to cell biological, to investigate kinesin motors from the single molecule to the cellular level. Relevant questions include: How do kinesin motors bind their cargoes and become activated for transport? How do kinesin motors navigate the complex microtubule network in cells? How do multiple motors on the surface of a cargo coordinate their activities ...

The motor protein kinesin is a dimer with two identical motor heads. Each head consists of a catalytic core and a neck linker. In the cell, kinesins pull organelles along microtubule tracks. The organelle attaches to the other. ...

The cytoskeleton is not permanent; rather it assembles and disassembles as needed at the various locales within the cytoplasm. The cytoskeleton also serves as a railway system of sorts, used by the cells machinery to ferry organelles and other cellular cargo from place to place within the cell.. Several different proteins function as molecular motors transporting cargo along the cytoskeletal tracks. This list includes myosin, dynein, and kinesin. Myosin moves cellular material along actin filaments or microfilaments. Both dynein and kinesin haul their loads on microtubule tracks.. Kinesins structure resembles two golf clubs with their shafts intertwined around one another in a helical fashion. Attached to kinesins rod-like region are two lobe-shaped structures that resemble the heads of golf clubs.. The kinesin heads interact with microtubules. The rod-like shaft binds the cellular cargo that kinesin will transport along the microtubules. Kinesin moves along the microtubules by walking ...

TY - JOUR. T1 - Kinesin and dynein-dynactin at intersecting microtubules. T2 - Motor density affects dynein function. AU - Ross, Jennifer L.. AU - Shuman, Henry. AU - Holzbaur, Erika L.F.. AU - Goldman, Yale E.. N1 - Funding Information: This work was supported by the National Institutes of Health (NIH) project program grant P01-AR-051174 to the Pennsylvania Muscle Institute, National Science Foundation grant NSEC DMR04-25780 to the Penn Nano/Bio Interface Center, and by NIH GM068591 to E.L.F.H. J.L.R. was supported by an NIH National Research Service Award grant 1F32GM075754-01. The authors have no competing interests. PY - 2008/4/15. Y1 - 2008/4/15. N2 - Kinesin and cytoplasmic dynein are microtubule-based motor proteins that actively transport material throughout the cell. Microtubules can intersect at a variety of angles both near the nucleus and at the cell periphery, and the behavior of molecular motors at these intersections has implications for long-range transport efficiency and ...

Kidney ankyrin repeat-containing proteins (KANK1/2/3/4) belong to a family of scaffold proteins, playing critical roles in cytoskeleton organization, cell polarity and migration. Mutations in KANK proteins are implicated in cancers and genetic diseases, such as nephrotic syndrome. KANK proteins can bind various target proteins through different protein regions, including a highly conserved ankyrin repeat domain (ANKRD). However, the molecular basis for target recognition by the ANKRD remains elusive. In this study, we solved a high-resolution crystal structure of the ANKRD of KANK1 in complex with a short sequence of the motor protein kinesin family member 21A (KIF21A), revealing that the highly specific target-binding mode of the ANKRD involves combinatorial use of two interfaces ...

Solution 3 (EMS +2FOC on the shoulder and on the upperarm) HALLOW SHAFT MOTOR J1 J2J3 ELBOW HAND ETH_IN ETH_OUT PS_DC_MOTORS CAN_SKIN2 CAN_FTSENSOR ETH_IN ETH_OUT PS_DC_MOTORS CAN_SKIN2 CAN_FTSENSOR ETH_IN ETH_OUT PS_DC_MOTORS PS_BLDC_MOTORS ETH_IN ETH_OUT PS_DC_MOTORS PS_BLDC_MOTORS ETH_IN ETH_OUT PS_DC_MOTORS PS_BLDC_MOTORS CAN_FTSENSORS 2 Absolute encoder 1 incremental enc 1 hall phase 1 motor phase 1 CAN_SKIN ETH_IN ETH_OUT PS_DC_MOTORS PS_BLDC_MOTORS CAN_FTSENSORS 2 Absolute encoder 1 incremental enc 1 hall phase 1 motor phase 1 CAN_SKIN ETH_IN ETH_OUT PS_DC_MOTORS PS_BLDC_MOTORS CAN_FTSENSORS 1 HALL sensor 1 MOTOR PHASE 1 Absolute encoder ETH_IN ETH_OUT PS_DC_MOTORS PS_BLDC_MOTORS CAN_FTSENSORS 1 HALL sensor 1 MOTOR PHASE 1 Absolute encoder ETH_IN ETH_OUT PS_DC_MOTORS PS_BLDC_MOTORS CAN_FTSENSORS ETH_IN ETH_OUT PS_DC_MOTORS PS_BLDC_MOTORS CAN_FTSENSORS

Intercalation movement of proliferative chondrocytes is crucial for their columnar organization which is essential for proper function of growth plate cartilage. The conventional motor protein kinesin‐1 directionally transporting various cargos along microtubules might be involved in this polarized cell movement. Kinesin‐1 is suggested to transport unknown cargo(s) modulating focal adhesion (FA) turnover which is a key step in cell movement. To investigate kinesin‐1s role in chondrocytes intercalation, we generate kinesin‐1 heavy chain (Kif5b) knockout mouse. In the growth plate of KIF5B deficient mouse, we observed abnormal cell morphology and disrupted columnar structure. Isolated mutant chondrocytes show reduced motility and adhesion ability to ECM proteins. Vinculin, the key regulator of focal adhesions, is found as a potential protein associated with KIF5B in mouse chondrocytes. Further study will investigate whether KIF5B affects chondrocytes motility and adhesion via FAs ...

Cyclin-dependent kinase 5 (cdk5) inhibits neurofilament (NF) anterograde axonal transport while p42/44 mitogen-activated protein kinase (MAPk) promotes it. Since cdk5 is known to inhibit MAP kinase activity, we examined whether or not cdk5 inhibits anterograde NF transport via inhibition of MAPk activity. To accomplish this, we manipulated the activity of these kinases in differentiated NB2a/d1 cells, and monitored anterograde axonal transport of green fluorescent protein-conjugated-NF-M (GFP-M) and cyan fluorescent protein-conjugated (CFP)-tau. The cdk5 inhibitor roscovitine increased anterograde axonal transport of GFP-M and CFP-tau; transfection with cdk5/p25 inhibited transport of both. Inhibition of MAPk activity by PD98059 or expression of dominant-negative MAPk inhibited anterograde GFP-M transport, while expression of constitutively active MAPk enhanced it; these treatments did not affect CFP-tau transport. PD98059 prevented roscovitine-mediated enhancement of GFP-M transport, but did ...

TY - JOUR. T1 - Microfabricated capped channels for biomolecular motor-based transport. AU - Huang, Ying Ming. AU - Uppalapati, Maruti. AU - Hancock, William O.. AU - Jackson, Thomas Nelson. PY - 2005/11/1. Y1 - 2005/11/1. N2 - Kinesins are molecular motors that transport intracellular cargo along microtubules and provide a model system for force generation that can be exploited for biomotor powered nano- and micro-machines. To use this biological system for microscale transport, the most common approach is to reverse the biological geometry and move microtubules along surfaces functionalized with kinesin motors. The microtubules then become potential transport vehicles for sensors and lab-on-a-chip applications. A key requirement for extracting useful work from this system is confinement and control of microtubule movements over kinesin-coated surfaces. The open channel approaches used to date are limited because microtubules that lose contact with the kinesin motors rapidly diffuse away. As a ...

Reorganization of the oocyte microtubule cytoskeleton during mid-oogenesis results in an apparent AP gradient of microtubules (Theurkauf et al., 1992). A longstanding model proposed that these microtubules are polarized along the AP axis, with minus ends nucleated at the anterior cortex and plus ends projected towards the posterior. Accordingly, whether an RNP particle is transported to the anterior or posterior pole would depend on whether it associates with dynein or kinesin motor proteins. This model is based on a number of observations. First, partial microtubule depolymerization leaves short microtubules associated with the anterior cortex (Theurkauf et al., 1992). Because microtubules depolymerize from the plus end, this result suggests that microtubules are nucleated at the anterior cortex. Furthermore, a fusion between the motor domain of kinesin and β-galactosidase (kinesin-β-gal) that localizes to the plus ends of microtubules in neurons (Giniger et al., 1993) accumulates at the ...

An essential role for the primary cilium in Hh pathway and Gli protein activation has been well established by numerous genetic studies in various vertebrate species in the past decade (Nozawa et al., 2013). However, the role of the ciliary localization of Gli proteins in their activation has not yet been determined. One commonly taken approach to address this issue has been to disrupt the cellular and/or ciliary transport machinery. In one such study, the disruption of the cytoplasmic microtubule network through a drug treatment abolished the ciliary localization of Gli2 and disrupted the Hh signaling (Kim et al., 2009). Similarly, mutations in a microtubule motor protein Kif7, or in an intraflagellar transport protein Ift25, affected Gli2 ciliary localization and Hh pathway activation (Cheung et al., 2009; Endoh-Yamagami et al., 2009; He et al., 2014; Keady et al., 2012; Liem et al., 2009). One major concern with this approach is that additional proteins and processes affected by the ...

What function might a flagellar membrane-associated CrKCBP have? One function might include a role in intraflagellar transport (IFT). IFT involves a plus-end-directed heterotrimeric kinesin as well as a minus-end-directed cytoplasmic dynein and is required for the assembly, disassembly and structural maintenance of cilia and flagella (for a review, see Cole, 2003). Presumably, a minus-end-directed kinesin (CrKCBP) and cytoplasmic dynein would have redundant functions in IFT. However, it is possible that two minus-end-directed motors are required during rapid flagellar resorption. In Chlamydomonas, flagellar resorption can be induced by removal of Ca2+ from the medium and is reversed by re-addition of Ca2+ to the medium (Lefebvre et al., 1978). If CrKCBP is negatively regulated by Ca2+-calmodulin in the same way as AtKCBP (see Song et al., 1997), removal of Ca2+ from the medium would activate KCBP, consistent with a role for CrKCBP during flagellar resorption.. Several key observations provide ...

TY - JOUR. T1 - Hedgehog elicits signal transduction by means of a large complex containing the kinesin-related protein costal2. AU - Robbins, David J.. AU - Nybakken, Kent E.. AU - Kobayashi, Ryuji. AU - Sisson, John C.. AU - Bishop, J. Michael. AU - Thérond, Pascal P.. N1 - Funding Information: We thank M. Scott, T. Kornberg, R. Vale, C. Walczak, K. Hill, A. Capobianco, Q. Guo, D. Casso, and other members of the Bishop and Kornberg laboratories for helpful discussions. This work was supported by funds from the National Institutes of Health (CA44338 for J. M. B. and CA45508 for R. K.) and the G.W. Hooper Research Foundation. D. J. R. was supported by the American Cancer Society (PF-4144). J. S. was an associate of the Howard Hughes Medical Institute. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.. PY - 1997/7/25. Y1 - 1997/7/25. N2 - The hedgehog gene of Drosophila melanogaster encodes a secreted protein (HH) that plays a vital role in cell fate and patterning. Here we describe ...

Filanesib, also known as ARRY-520 is a synthetic, small molecule targeting the kinesin spindle protein (KSP) with potential antineoplastic activity. KSP inhibitor ARRY-520 specifically inhibits KSP (kinesin-5 or Eg5), resulting in activation of the spindle assembly checkpoint, induction of cell cycle arrest during the mitotic phase, and consequently cell death in tumor cells that are actively dividing. Because KSP is not involved in postmitotic processes, such as neuronal transport, this agent does not cause the peripheral neuropathy that is often associated with tubulin-targeting agents. KSP is an ATP-dependent microtubule motor protein that is essential for the formation of bipolar spindles and the proper segregation of sister chromatids during mitosis....

This years winner of the WIC Culture of Writing Award in Physics is Jeremy Meinke, for his thesis entitled, Single-Molecule Analysis of a Novel Kinesin Motor Protein. Jeremy worked under the direction of Prof. Weihong Qiu. He was with the Qiu research group for two years and in 2016, he received URISC and SURE awards to support his work. Jeremy says of the OSU Physics Department, I enjoyed the range of physics topics the upper division classes offered, which kept me constantly thinking about new concepts. Overall, it was a great place for me to study physics. I truly benefited from the research experience.. Research in Prof. Qius lab is mainly focused on understanding the mechanism and regulation of kinesins, motor proteins that transform chemical energy into mechanical work to move on train track-like structures called microtubules inside the cells. For his senior thesis, Jeremy used total internal reflection fluorescence microscopy to show that BimC - a particular kinesin from the ...

Kinesin Family Member 20A) is a Protein Coding gene. Diseases associated with KIF20A include Familial Isolated Restrictive Cardiomyopathy. Among its related pathways are PLK1 signaling events and Factors involved in megakaryocyte development and platelet production. Gene Ontology (GO) annotations related to this gene include protein kinase binding and ATPase activity. An important paralog of this gene is KIF23 ...

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Centrosome-associated protein E (CENPE) is a kinesin-like motor protein that accumulates in the G2 phase of the cell cycle. Unlike other centrosome-associated proteins, it is not present during interphase and first appears at the centromere region of chromosomes during prometaphase. This protein is required for stable spindle microtubule capture at kinetochores which is a necessary step in chromosome alignment during prometaphase. This protein also couples chromosome position to microtubule depolymerizing activity. Alternative splicing results in multiple transcript variants encoding distinct protein isoforms. [provided by RefSeq, Nov 2014 ...

Trypanosoma brucei ist ein einzelliger Parasit, der eine Flagelle besitzt. Er verursacht südlich der Sahara die afrikanische Trypanosomiasis, die allgemein als Schlafkrankheit bekannt ist. Eine anspruchsvolle Aufgabe beim Bekämpfen dieser Krankheit ist es, neue Medikamente zu finden, die ohne schwerwiegende Nebenwirkungen für den Patienten sowie einfach zu verabreichen sind. Diese Arbeit betrachtet das mitotische Kinesin TbKif13-1 als ein potentielles Angriffsziel für Medikamente. Es wurde versucht, die Vorraussetzungen für eine in vivo und eine in vitro Suche nach einem TbKif13-1 Inhibitor im Hochdurchsatz mit automatisierter Bildanalyse zu schaffen. Die Grundlage beider Analysemethoden war die durch TbKif13-1 vermittelte Depolymerisation von Mikrotubuli und deren Verhinderung durch einen passenden Inhibitor. Im in vivo Versuchsaufbau diente das Mikrotubulizytoskelett von HeLa Zellen in Interphase als Substrat. Die Vorraussetzung für diesen Versuch war eine stabile HeLa Zelllinie, die ...

Proteins at interfaces play a major role in biomaterials and lab-on-a-chip devices. Protein interactions with the surface change their conformations and therefore their ability to bind to their respective ligands. Another major area of interest surrounding biomaterials and lab-on-a-chip devices is the prediction and prevention of wear. Wear is the progressive loss of material from an object caused by contact and relative movement of the contacting solid, liquid, or gas. It is estimated that wear costs 1% of the gross domestic product (approximately $150 billion for the US). With the emergence of drug-releasing implants and lab-on-the-chip devices, wear has also become a major concern in bio- and nano- technology. In our laboratory, we use microtubules (filamentous proteins) gliding on kinesin motor proteins as transporters in biosensors. This system, known as the motility assay, is ideal for studying how the conformation of kinesins impacts the gliding of microtubules and therefore the performance of

Smoothened is a G protein-coupled receptor protein encoded by the SMO gene of the hedgehog signaling pathway conserved from flies to humans. It is the molecular target of the teratogen cyclopamine. Cellular localization plays an essential role in the function of SMO. Stimulation of the patched receptor by the sonic hedgehog ligand leads to translocation of SMO to the primary cilium. Furthermore, SMO that is mutated in the domain required for ciliary localisation cannot contribute to pathway activation.[3] SMO has also been shown to bind the kinesin motor protein Costal-2 and play a role in the localization of the Ci (Cubitus interruptus transcription factor) complex. SMO can function as an oncogene. Activating SMO mutations can lead to unregulated activation of the hedgehog pathway and cancer.. ...

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.

Abstract Background Kinesin spindle proteins (KSP) are motor proteins that play an essential role in mitotic spindle formation. HsEg5, a KSP, is responsible for the formation of the bipolar spindle, which is critical for proper cell division during mitosis. The function of HsEg5 provides a novel target for the manipulation of the cell cycle and the induction of apoptosis. SB715992, an experimental KSP inhibitor, has been shown to perturb bipolar spindle formation, thus making it an excellent candidate for anti-cancer agent. Our major objective was a) to investigate the cell growth inhibitory effects of SB715992 on PC-3 human prostate cancer cell line, b) to investigate whether the growth inhibitory effects of SB715992 could be enhanced when combined with genistein, a naturally occurring isoflavone and, c) to determine gene expression profile to establish molecular mechanism of action of SB715992. Methods PC-3 cells were treated with varying concentration of SB715992, 30 μM of genistein, and SB715992

doc, Research in my laboratory focuses on spindle and chromosome dynamics and the mechanisms that ensure proper chromosome transmission and inheritance in dividing cells. Work in my laboratory and others over the past 5-10 years has identified molecular motor proteins as the force-generating proteins underlying movements of the spindle and chromosomes during cell division. Much of our current effort is directed towards understanding the mechanism of motor function, including the molecular basis of motor directionality, and the contribution of motor proteins to spindle and chromosome dynamics in living cells. ,br/, ,br/,During the past several years, we have used molecular genetics to determine the basis of the reversed directionality compared to kinesin of the Ncd motor protein, discovered in my laboratory. Ncd is a microtubule motor that is required for proper spindle assembly in oocytes and early embryos of Drosophila. We showed previously that Ncd moves on microtubules in the opposite ...

In regulated exocytosis, vesicles are stored in the cytoplasm and are moved to specific plasma membrane regions after the cell receives a signal. So, it is a regulated process not only temporally but also spatially. Neurons show a good example of regulated exocytosis. In these cells, some vesicles are formed around the nucleus, in the soma, and are moved to the presynaptic terminal, which can be several centimeters away from the soma. These vesicles fuse with the presynaptic membrane after the arriving of an action potential. Other polarized cells are the enterocytes of the intestine epithelium, which have an apical domain facing the lumen of the intestine and a basolateral domain. It would be a catastrophe if vesicles loaded with digestive enzymes are released to the basolateral domains because the surrounding tissue would be digested. These vesicles are moved to the correct domain of the membrane, the apical one, by microtubules of the cytoskeleton, helped by kinesin motor proteins. ...

Spheroid colony formation is a typically method to identify cancer stem cells (CSC). The growth of spherical colonies is considered indicative of self-renewal ability, and is consistent with a CSC phenotype. However, mechanism of spheroid formation remains unclear in gastric cancer (GC). In the present study, we analyzed spheroid formation associated genes in GC. Comprehensive gene expression profile of MKN-45 and MKN-74 GC cell lines that were grown as monolayers or spheroids was obtained by Affymetrix GeneChip, and we found several kinds of genes whose expression was up-regulated or down-regulated in cells that were grown as spheroids. Among these, 10 kinds of kinesin genes were up-regulated in both MKN-45 and MKN-74 cells that were grown as spheroids. Kinesins are categorized into 14 subfamilies and classified as mitotic kinesins, which are involved in cell division, and non-mitotic kinesins, which are principally involved in intracellular transport. In spheroids, mitotic kinesins were ...

Cell microtubules, anaglyph 3D animation. Clip 4 of 10. This clip forms part of an animation sequence showing protein interactions within a dividing cell. This clip shows the microtubules of the cells cytoskeleton, surrounded by proteins in the cytoplasm, with the motor protein kinesin 8 moving along the microtubles. The full sequence of ten clips shows the interaction between the protein calmodulin (CaM, calcium-modulated protein), calcium ions, the MLCK (myosin light-chain kinase) protein, and the actin-myosin bundles of the cells cytoskeleton, resulting in contraction of the membrane and cell division. To see this clip in 3D, please view using red-blue glasses, with red on the left. For the entire sequence, see clips K003/4492 to K003/4483. For the same sequence as an ordinary animation with labels, see clips K003/3847 to K003/3838. - Stock Video Clip K003/4489

Although assembly of the mitotic spindle is known to be a precisely controlled process, regulation of the key motor proteins involved remains poorly understood. In eukaryotes, homotetrameric kinesin-5 motors are required for bipolar spindle formation. Eg5, the vertebrate kinesin-5, has two modes of motion: an adenosine triphosphate (ATP)-dependent directional mode and a diffusive mode that does not require ATP hydrolysis. We use single-molecule experiments to examine how the switching between these modes is controlled. We find that Eg5 diffuses along individual microtubules without detectable directional bias at close to physiological ionic strength. Eg5s motility becomes directional when bound between two microtubules. Such activation through binding cargo, which, for Eg5, is a second microtubule, is analogous to known mechanisms for other kinesins. In the spindle, this might allow Eg5 to diffuse on single microtubules without hydrolyzing ATP until the motor is activated by binding to another ...

Jennifer Ross, University of Massachusetts Single Molecule Biophysics: Cellular Highways and Big Rigs Microtubules form a polarized network that is primarily radial, but microtubules intersect at a variety of angles both near the nucleus and at the cell periphery. The behavior of kinesin and dynein at these intersections may affect long-range transport efficiency, targeting, and accuracy. Intersecting microtubules serve as crossroads and also possibly as obstacles. In order to test motor function at microtubule intersections, cross-overs of microtubule tracks were arranged in vitro using flow to orient successive layers of filaments. Single molecules of GFP-labeled kinesin and cytoplasmic dynein-dynactin-GFP were observed using total internal reflection fluorescence microscopy. Motors were also bound to artificial bead cargos at various concentrations. Dynein-dynactin coated beads exhibited a strong dependence on motor density. At low density, the behavior at intersections was highly variable, ...

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Depletion of endogenous huntingtin disrupts axonal transport of APP in primary cortical neurons (Fig. 1). Together with previous findings in Drosophila and mouse neurons (Gunawardena et al., 2003; Gauthier et al., 2004; Trushina et al., 2004), these data establish that endogenous huntingtin is required for axonal transport of a variety of cargoes including APP, BDNF, and mitochondria in various types of neurons. However, the exact role of huntingtin in axonal transport remains unclear. Although huntingtin interacts with dynein intermediate chain, p150Glued, and kinesin light chain, loss of huntingtin does not affect either the level of or complexes of huntingtin, HAP1, dynactin, and kinesin-I (Figs. 2, 7A). Thus, dysfunction of axonal transport in the absence of huntingtin is not attributable to a disruption of motor protein complexes, but instead may result from altered regulation of intact complexes. Moreover, in contrast to published data (Gauthier et al., 2004), no changes in the biochemical ...

She is a senior research scientist at Biologic Institute. Her work uses molecular genetics and genomic engineering to study the origin, organization and operation of metabolic pathways. She received a BS in biology from MIT, and a PhD in developmental biology from the University of Washington, where she studied cell adhesion molecules involved in Drosophila embryogenesis. As a post-doctoral fellow at Harvard she cloned and characterized the Drosophila kinesin light chain. Her research has been published in Nature, Development, and the Journal of Biological Chemistry. ...

The ability of a neuron to regulate steady-state expression and transport dynamics of mRNA granules in axons and dendrites is believed to be modulated by mRNA binding proteins acting as adapters for molecular motors. While previous work has shown that ZBP1-mediated localization of β-actin mRNA into axons depends on microtubules (Zhang et al., 1999, 2001), it remains unclear what molecular motors are involved in the directed transport of ZBP1. Kinesin motors have been shown to play an important role in the transport of mRNAs and mRNA binding proteins in neurons (Kanai et al., 2004; Dictenberg et al., 2008). In these studies, perturbation of kinesin leads to a reduction in RNA granule localization in neuronal processes and impaired dynamics. Here, we report that perturbation of myosin Va leads to an opposite phenotype, characterized by increased levels and transport dynamics of ZBP1 in axons. These findings suggest that transport dynamics for ZBP1 and perhaps other mRNA granule components are ...

Joachim Frank (Columbia University, New York, USA) is a pioneer of single particle reconstruction, which is the most used reconstruction method for 3DEM structures in EMDB and EM entries in PDB. And also, he is a develper of Spider, which is one of the most famous software in this field, and is used for some EM Navigor data (e.g. map projection/slice images ...

Abstract. Abstract 1868Background. ARRY-520 is a kinesin spindle protein (KSP) inhibitor that has demonstrated clinical activity in patients with relapsed and

Background: ALN-VSP02 is a RNA interference (RNAi) therapeutic comprised of lipid nanoparticle-formulated small interfering RNAs (siRNAs) targeting the expression of vascular endothelial growth factor (VEGF)-A and kinesin spindle protein (KSP). Methods: A multi-center, open label, phase I dose-escalation trial of ALN-VSP02 administered as a 15-minute iv infusion q2 wks was initiated in patients (pts) with advanced solid tumors and at least one measurable liver lesion. Main objectives included evaluation of safety/tolerability and assessment of PK/PD. Results: Thirty-one pts were enrolled across 7 dose levels (0.1-1.5 mg/kg); median age 57 yrs, all with multiple prior therapies. A total of 140 doses were administered, mean of 4.5 (range 1-17). Treatment was generally well-tolerated, with no dose-dependent trends in clinical or laboratory adverse events. One on-study death (liver failure in a pt with near complete replacement of the liver by tumor) deemed possibly related to treatment occurred at ...

UPS is ordering 10 electric aircraft that are designed to take off and land like a helicopter, allowing it to fly cargo directly between its facilities in small markets and bypass airports.

Delivering therapeutics deep into damaged tissue during bleeding is challenging because of the outward flow of blood. When coagulants cannot reach and clot blood at its source, uncontrolled bleeding can occur and increase surgical complications and fatalities. Self-propelling particles have been proposed as a strategy for transporting agents upstream through blood. Many nanoparticle and microparticle systems exhibiting autonomous or collective movement have been developed, but propulsion has not been used successfully in blood or used in vivo to transport therapeutics. We show that simple gas-generating microparticles consisting of carbonate and tranexamic acid traveled through aqueous solutions at velocities of up to 1.5 cm/s and delivered therapeutics millimeters into the vasculature of wounds. The particles transported themselves through a combination of lateral propulsion, buoyant rise, and convection. When loaded with active thrombin, these particles worked effectively as a hemostatic agent ...

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Research in our lab is focused on motor proteins, which are molecular machines that drive cargo along tracks to specific sites in the cell, like a train running along a railway network to its specific destinations. New results now show that these molecular motor proteins may play a crucial role in the pathway that eliminates damaged mitochondria. In this project, we will use a number of techniques to identify how these motor proteins or its cargo hooks associate with the machinery that mediates cellular quality control. In addition, we will test whether eliminating the molecular motors inhibits turnover of damaged cell parts leading to an accumulation of non-functional mitochondria and reduced energy production. Relevance to Diagnosis/Treatment of Parkinson s Disease ...

We computationally model the kinesin chemomechanical cycle in order to: 1) motivate and interpret our experiments, 2) test hypotheses, and 3) gain intuitive insights into mechanics at the nano scale. We have used stochastic (Monte Carlo) models of the kinesin hydrolysis cycle to understand how intermolecular tension controls processivity and interpret our single-molecule data (1,2). To understand diffusive aspects of the free head stepping to the next binding site, we have carried out Brownian Dynamics models that incorporate tethered diffusion (3). To understand the mechanics of the neck linker domain, we have carried out Molecular Dynamics simulations of neck linker pulling (4). Finally, we are working with John Fricks (PSU Statistics) to develop novel approaches to modeling the hydrolysis cycle (5,6). ...

TY - JOUR. T1 - Paclitaxel targets FOXM1 to regulate KIF20A in mitotic catastrophe and breast cancer paclitaxel resistance. AU - Khongkow, P.. AU - Gomes, A. R.. AU - Gong, C.. AU - Man, E. P.S.. AU - Tsang, J. W.H.. AU - Zhao, F.. AU - Monteiro, L. J.. AU - Coombes, R. C.. AU - Medema, R. H.. AU - Khoo, U. S.. AU - Lam, E. W.F.. PY - 2016/2/25. Y1 - 2016/2/25. N2 - All rights reserved. FOXM1 has been implicated in taxane resistance, but the molecular mechanism involved remains elusive. In here, we show that FOXM1 depletion can sensitize breast cancer cells and mouse embryonic fibroblasts into entering paclitaxel-induced senescence, with the loss of clonogenic ability, and the induction of senescence-associated β-galactosidase activity and flat cell morphology. We also demonstrate that FOXM1 regulates the expression of the microtubulin-associated kinesin KIF20A at the transcriptional level directly through a Forkhead response element (FHRE) in its promoter. Similar to FOXM1, KIF20A expression ...

Igor M. Kulić, André E. X. Brown, Hwajin Kim, Comert Kural, Benjamin Blehm, Paul R. Selvin, Philip C. Nelson and Vladimir I. Gelfand ...

Cilia are microtubule based structures that can be motile or immotile, the latter being referred to as primary cilia. In contrast to motile cilia, such as those found on epithelia of the trachea, the importance of the primary cilium is relatively undefined despite their presence on most mammalian cells. Cilia are extremely complex organelles which are devoid of ribosomes, thus, proteins required for cilia assembly, maintenance, and signaling must be imported into the cilium. This occurs through a microtubule-based transport system called intraflagellar transport (IFT). Proteins involved in IFT concentrate around the basal body at the base of the cilium and assemble into complexes (IFT particles) which are moved up the cilium by a kinesin and returned by a cytoplasmic dynein. The IFT particle is thought to mediate the transport of cargo into the cilium as well as to deliver signals initiated in the cilium to the cytosol. Although the primary cilium was once thought to be a vestigial organelle, ...

Cytoplasmic dynein and kinesin-1 are opposite-polarity, microtubule-based motors that transport a wide variety of cargo in eukaryotic cells. Many cellular cargos demonstrate bi-directional movement due to the presence of ensembles of dynein and kinesin but are ultimately sorted with spatial and temporal precision. To investigate the mechanisms that coordinate motor ensemble behavior, we built a programmable synthetic cargo using three-dimensional DNA origami to which varying numbers of DNA oligonucleotide-linked motors could be attached, allowing control of motor type, number, spacing, and orientation in vitro. In ensembles of 1-7 identical-polarity motors, motor number had minimal affect on directional velocity, while ensembles of opposite-polarity motors engaged in a tug-of-war resolvable by disengaging one motor species.. ...

Bipolar spindle assembly and failure of chromatin stretching in oocytes expressing αtub67CP40. A, Drosophila female meiotic spindles were examined by indirect