• We investigated whether the formation of aggresomes affected key centrosome functions: its ability to organize the microtubule network and to promote cilia formation. (biorxiv.org)
  • Multiple expansion microscopy approaches have been successfully used in the analysis of centrioles, centrosomes, and cilia, helping to reveal the localization of numerous centrosomal and ciliary proteins at nanoscale resolution. (bvsalud.org)
  • The pivotal structure of the primary cilia is a microtubule that is generated via tubulin polymerization reaction that occurs in the basal body. (biomedcentral.com)
  • Within the cell, the arrangement of microtubules is controlled by a variety of discreet microtubule-organizing centers (MTOCs), but in most cells, the dominant MTOC is the centrosome, a bipartite structure consisting of a central pair of barrel-shaped centrioles and a surrounding matrix of pericentriolar material (PCM). (nih.gov)
  • In the past several years it has become apparent that defects in centrosomes and centrioles are linked to, and even causative of, a growing number of human diseases including cancer, microcephaly, and dwarfism. (nih.gov)
  • The centrioles contain nine microtubule triplets and mature into a centrosome that is referred to as a basal body in the context of ciliogenesis [ 22 , 23 ]. (biomedcentral.com)
  • The early cells of the pre-implantation mouse embryo utilise a unique non-centrosomal MTOC, in the form of an interphase microtubule bridge joining sister cells. (wikipedia.org)
  • The two antiparallel MTs that make up each bundle overlap at their minus ends at the interphase microtubule organizing center (iMTOC), which attaches to the nuclear envelope. (rupress.org)
  • The centrosome is the most common MTOC for multipotent cells in animals, with differentiated tissues utilising a wide variety of non-centrosomal MTOCs. (wikipedia.org)
  • Some cells however, such as those of higher plants and oocytes, lack distinct MTOCs and microtubules are nucleated via a non-centrosomal pathway. (wikipedia.org)
  • These non-centrosomal microtubule arrays can take on various geometries-such as those leading to the long, slender shape of myotubes, the fine protrusions of an axon, or the strongly polarized domains of an epithelial cell. (wikipedia.org)
  • These branching microtubules maintain the same polarity as their mother microtubules, and their assembly involves the binding of non-centrosomal γ-TuRCs to the sides of existing microtubules through the augmin complex. (wikipedia.org)
  • Myomegalin is necessary for the formation of centrosomal and Golgi-derived microtubules. (crcm-marseille.fr)
  • Together with dynactin, dynein regulates centrosomal orientation to establish and maintain cell polarity, controls focal adhesion turnover and anchors microtubules at the leading edge. (biologists.com)
  • Microtubule nucleation occurs spontaneously in vitro, with solutions of purified tubulin giving rise to full-length polymers. (wikipedia.org)
  • The primary pathway by which microtubule nucleation is assisted requires the action of a third type of tubulin, γ-tubulin, which is distinct from the α and β subunits that compose the microtubules themselves. (wikipedia.org)
  • This complex, with its 13-fold symmetry, acts as a scaffold or template for α/β tubulin dimers during the nucleation process-speeding up the assembly of the ring of 13 protofilaments that make up the growing microtubule. (wikipedia.org)
  • Five proteins in Drosophila (DGT2 through DGT6) have been identified that are necessary and responsible for facilitating the localization of γ-tubulin to existing MTs and are not associated with its localization at the centrosome. (wikipedia.org)
  • The generation of cellular microtubules is initiated at specific sites such as the centrosome and the Golgi apparatus that contain nucleation complexes rich in γ-tubulin. (crcm-marseille.fr)
  • One isoform, CM-MMG, harbors a conserved domain (CM1), recently described as a nucleation activator, and is related to a family of γ-tubulin binding proteins, which includes Drosophila centrosomin. (crcm-marseille.fr)
  • It recruits γ-tubulin nucleating complexes and promotes microtubule nucleation. (crcm-marseille.fr)
  • This creates new nucleation sites for more MTs, thanks to the activities of γ-tubulin and a MT-associated protein called mto2p.Fission yeast have a simple, consistent interphase MT arrangement composed of four bundles per cell. (rupress.org)
  • In this study, we identify a previously uncharacterised isoform of microtubule-associated protein MAP4, oMAP4, as a microtubule organising factor that is crucial for myogenesis. (elifesciences.org)
  • We find that when aggresomes are present, neuronal cells are unable to organise their microtubule network. (biorxiv.org)
  • Since dopaminergic neurons are polarised, ensuring correct localisation of organelles and the effective intracellular transport of neurotransmitter vesicles, loss of centrosome activity could contribute to loss of dopaminergic function and neuronal cell death in Parkinson's disease. (biorxiv.org)
  • Several lines of evidence suggest that microtubules are nucleated at the neuronal centrosome, and then released for transport into axons and dendrites. (silverchair.com)
  • Here we sought to determine whether the microtubule-severing protein known as katanin mediates microtubule release from the neuronal centrosome. (silverchair.com)
  • These results indicate that microtubule-severing by katanin is essential for releasing microtubules from the neuronal centrosome, and also for regulating the length of the microtubules after their release. (silverchair.com)
  • Among its other functions, this radial array is used by microtubule-based motor proteins to transport various cargoes, such as vesicles, to the plasma membrane. (wikipedia.org)
  • In the cortical array of plants, as well as in the axons of neurons, it is theorised that microtubules nucleate from existing microtubules via the action of severing enzymes such as katanin. (wikipedia.org)
  • Immunomicroscopic analyses on cultured sympathetic neurons show that katanin is present at the centrosome, but is also widely distributed throughout the neuron. (silverchair.com)
  • Microinjection of an antibody that inactivates katanin results in a dramatic accumulation of microtubules at the centrosome, indicating that katanin is indeed required for microtubule release from the centrosome. (silverchair.com)
  • It may be that katanin severs microtubules throughout the cell body to keep them sufficiently short to be efficiently transported into developing processes. (silverchair.com)
  • Consistent with this idea, there were significantly fewer free ends of microtubules in the cell bodies of neurons that had been injected with the katanin antibody compared with controls. (silverchair.com)
  • Through use of TIRF microscopy, researchers have visually observed the nucleation of branching microtubules in Drosophila cells during the formation of the mitotic spindle. (wikipedia.org)
  • In toto , our results show that the connection between centrosomes and chromosomes is mediated by an anchoring into the entire spindle network and that any direct connections through KMTs are few and likely very transient. (nature.com)
  • The mitotic spindle is a dynamic microtubule-based apparatus that ensures the segregation of chromosomes during cell division. (nature.com)
  • Remarkably, despite the high turnover of microtubules throughout mitosis 2 , the spindle maintains its bipolar structure with the chromosomes at its center and two poles that are separated by the plane of cell division. (nature.com)
  • If the role of KMTs is to mediate forces between chromosomes and spindle poles, they need to somehow connect to the centrosomes. (nature.com)
  • In the case of chromosomal origin, microtubules instead nucleate around chromosomes and only later attach to kinetochores, as observed in Xenopus cell-free extracts 13 . (nature.com)
  • Moreover, the implication that the active form of Ran is concentrated in the vicinity of chromosomes suggests that these findings may resolve the long-standing question of how chromosomes can influence spindle assembly in the absence of microtubule-nucleating organelles (i.e., as in plant mitosis or mammalian meiosis). (silverchair.com)
  • The γ-TuRC is typically found as the core functional unit in a microtubule organizing center (MTOC), such as the centrosome in some animal cells or the spindle pole bodies in fungi and algae. (wikipedia.org)
  • Depletion of PIP4KIIγ enhanced the spindle pole accumulation of mitotic centromere-associated kinesin (MCAK), a microtubule (MT)-depolymerizing kinesin, and resulted in a less stable spindle pole-associated MT. Depletion of MCAK can ameliorate PIP4KIIγ depletion-induced spindle abnormalities. (biomedcentral.com)
  • Here we combine the first large-scale serial electron tomography of whole mitotic spindles in early C. elegans embryos with live-cell imaging to reconstruct all microtubules in 3D and identify their plus- and minus-ends. (nature.com)
  • This cap provides both stability and protection to the microtubule (-) end from enzymes that could lead to its depolymerization, while also inhibiting (-) end growth. (wikipedia.org)
  • The spindle microtubule (MT) exhibits highly regulated dynamic instability, with frequent polymerization and depolymerization occurring at both the plus and minus ends. (biomedcentral.com)
  • New microtubules are not nucleated and extended, and the cells fail to respond to polarity cues. (biorxiv.org)
  • The microtubules within these processes have a consistent 13-protofilament lattice and are tightly regulated with regard to their polarity orientation. (silverchair.com)
  • Within the myoblasts, long filaments called microtubules are arranged in an overlapping linear pattern. (elifesciences.org)
  • used microscopy to observe the formation of the microtubule filaments in living myoblasts. (elifesciences.org)
  • The experiments also found that oMAP4 can create links between different microtubules and act as a brake to prevent the filaments being moved excessively by motor proteins. (elifesciences.org)
  • Akin to the action of cofilin in generating actin filament arrays, the severing of microtubules by MAPs creates new plus (+) ends from which microtubules can grow. (wikipedia.org)
  • In this fashion, dynamic arrays of microtubules can be generated without the aid of the γ-TuRC. (wikipedia.org)
  • Studies using Xenopus egg extracts have identified a novel form of microtubule nucleation that generates fan-like branching arrays, in which new microtubules grow at an angle off of older microtubules. (wikipedia.org)
  • A xons and dendrites contain dense arrays of highly organized microtubules. (silverchair.com)
  • We have proposed a model whereby these features of the axonal and dendritic microtubule arrays are established within the cell body of the neuron. (silverchair.com)
  • Microtubule (MT) arrays form, say Janson et al. (rupress.org)
  • The mutants were thus unable to nucleate new MTs after their arrays were depolymerized. (rupress.org)
  • Dynein is the sole processive minus-end-directed microtubule motor found in animals. (biologists.com)
  • Most notably, oMAP4 is required for paraxial microtubule organisation in muscle cells and prevents dynein- and kinesin-driven microtubule-microtubule sliding. (elifesciences.org)
  • We propose a model in which the cooperation of dynein-mediated microtubule transport and oMAP4-mediated zippering of microtubules drives formation of a paraxial microtubule array that provides critical support for the polarisation and elongation of myotubes. (elifesciences.org)
  • Branching MT nucleation has been observed in numerous organisms both in the plant and animal kingdoms. (wikipedia.org)
  • While our light microscopy and mutant studies show that microtubules are nucleated from the centrosomes, we find only a few KMTs directly connected to the centrosomes. (nature.com)
  • Indeed, by quantitatively analysing several models of microtubule growth, we conclude that minus-ends of KMTs have selectively detached and depolymerized from the centrosome. (nature.com)
  • We classify them as kinetochore (KMTs), spindle (SMTs) or astral microtubules (AMTs) according to their positions, and quantify distinct properties of each class. (nature.com)
  • The implications of those findings have influenced almost all further research of intracellular processes, including RAS signaling, immune synapses, DNA repair, transcriptional activation, and the functions of nuclear pores, the nucleolus and centrosomes. (hymanlab.org)
  • Therefore, the next challenge is to understand how other processes-such as the selective stabilisation of some microtubules and the movement of cell materials along the microtubules-cooperate to control muscle fibre formation. (elifesciences.org)
  • At least two of these have different roles, demonstrating a previously unknown mechanism to control microtubules in vertebrate cells. (crcm-marseille.fr)
  • In vivo, cells get around this kinetic barrier by using various proteins to aid microtubule nucleation. (wikipedia.org)
  • Depletion of Myomegalin by small interfering RNA delays microtubule growth from the centrosome and Golgi apparatus, and decreases directional migration of RPE1 cells. (crcm-marseille.fr)
  • The microtubules in cells that make smaller amounts of this protein were more disorganised, and these cells were unable to fuse with each other to form muscle cells. (elifesciences.org)
  • Despite the long-standing observation that aggresomes/Lewy bodies and the centrosome sit side-by-side in the cell, no studies have been done to see whether these protein accumulations impede the organelle function. (biorxiv.org)
  • The ultimate goal of my lab is to understand the molecular mechanisms that are used to control the number and size of centrosomes. (nih.gov)
  • While our understanding of centrosome biogenesis and function has advanced significantly in recent years, much still needs to be learned about how the number, size and activity of centrosomes are determined. (nih.gov)
  • Recent findings by several groups have shown that the GTP-bound form of Ran is necessary for the nucleation and organization of microtubule structures during M phase. (silverchair.com)
  • Upon differentiation, mono-nucleated myoblasts withdraw from the cell cycle and fuse to form syncytial myotubes ( Wakelam, 1985 ). (elifesciences.org)
  • The γ-TuRC also acts as a cap of the (−) end while the microtubule continues growth from its (+) end. (wikipedia.org)
  • In cell biology, microtubule nucleation is the event that initiates de novo formation of microtubules (MTs). (wikipedia.org)
  • Centrosome-independent spindle formation may thus also rely on MT-bound γ-TuCs. (rupress.org)
  • Second, we seek to understand how centrosome size and microtubule-organizing activity are controlled. (nih.gov)
  • It is one aim of our study to identify the nature of the KMT-centrosome connection in C. elegans , which is so far unknown. (nature.com)