Review Mechanisms and Molecules of the Mitotic Spindle
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Phosphorylation of the Microtubule-Severing AAA+ Enzyme Katanin Regulates C
Phosphorylation of the microtubule-severing AAA+ enzyme Katanin regulates C. elegans embryo development Nicolas Joly, Eva Beaumale, Lucie van Hove, Lisa Martino, Lionel Pintard To cite this version: Nicolas Joly, Eva Beaumale, Lucie van Hove, Lisa Martino, Lionel Pintard. Phosphorylation of the microtubule-severing AAA+ enzyme Katanin regulates C. elegans embryo development. Journal of Cell Biology, Rockefeller University Press, 2020, 219 (6), 10.1083/jcb.201912037. hal-03011242 HAL Id: hal-03011242 https://hal.archives-ouvertes.fr/hal-03011242 Submitted on 18 Nov 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. ARTICLE Phosphorylation of the microtubule-severing AAA+ enzyme Katanin regulates C. elegans embryo development Nicolas Joly, Eva Beaumale, Lucie Van Hove, Lisa Martino, and Lionel Pintard The evolutionarily conserved microtubule (MT)-severing AAA-ATPase enzyme Katanin is emerging as a critical regulator of MT dynamics. In Caenorhabditis elegans, Katanin MT-severing activity is essential for meiotic spindle assembly but is toxic for the Downloaded from https://rupress.org/jcb/article-pdf/219/6/e201912037/1044138/jcb_201912037.pdf by guest on 20 July 2020 mitotic spindle. Here we analyzed Katanin dynamics in C. elegans and deciphered the role of Katanin phosphorylation in the regulation of its activity and stability. -
Deciphering the Role of a Microtubule Severing Protein and a Protein Kinase in Cell Cycle and Ciliogenesis in Chlamydomonas Reinhardtii
DECIPHERING THE ROLE OF A MICROTUBULE SEVERING PROTEIN AND A PROTEIN KINASE IN CELL CYCLE AND CILIOGENESIS IN CHLAMYDOMONAS REINHARDTII by M. Qasim Rasi B.Sc., Simon Fraser University, 2004 THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY In the Department of Molecular Biology and Biochemistry ©M. Qasim Rasi 2009 SIMON FRASER UNIVERSITY Summer 2009 All rights reserved. This work may not be reproduced in whole or in part, by photocopy or other means, without permission of the author APPROVAL Name: M. Qasim Rasi Degree: Doctor of Philosophy Title of Thesis: Deciphering the role of a microtubule severing protein and a protein kinase in cell cycle and ciliogenesis in Chlamydomonas reinhardtii Examining Committee: Chair: Dr. C. Krieger Professor of Kinesiology _______________________________________________ Dr. Lynne Quarmby Senior Supervisor; Professor of Molecular Biology and Biochemistry _______________________________________________ Dr. Michel Leroux Supervisor; Associate Professor of Molecular Biology and Biochemistry _______________________________________________ Dr. Nick Harden Supervisor; Associate Professor of Molecular Biology and Biochemistry _______________________________________________ Dr. Christopher Beh Internal Examiner; Associate Professor of Molecular Biology and Biochemistry _______________________________________________ Dr. Stephen M. King External Examiner; Professor of Biochemistry, Associate Director, Graduate Program in Molecular Biology and Biochemistry, University of Connecticut Health Center Date Defended/Approved: June-5-2009 ii Declaration of Partial Copyright Licence The author, whose copyright is declared on the title page of this work, has granted to Simon Fraser University the right to lend this thesis, project or extended essay to users of the Simon Fraser University Library, and to make partial or single copies only for such users or in response to a request from the library of any other university, or other educational institution, on its own behalf or for one of its users. -
The Tumor Suppressor LZTS2 Functions Through the Cellular Samurai Katanin
Cent. Eur. J. Biol. • 4(1) • 2009 • 1–10 DOI: 10.2478/s11535-008-0063-0 Central European Journal of Biology The tumor suppressor LZTS2 functions through the cellular samurai Katanin Mini-Review Yoshiro Maru* Department of Pharmacology, Tokyo Womens Medical University, 162-8666 Tokyo, Japan Received 10 September 2008; Accepted 16 December 2008 Abstract: The leucine zipper putative tumor suppressor (LZTS) 2 is frequently and specifically found in LOH (loss of heterozygosity) analysis in cancer. Different from other LZTS family members, it regulates the microtubule-severing protein Katanin by binding the p80 regulatory subunit of Katanin and inhibiting its interaction with microtubules. At specific phases of the cell cycle, LZTS2 suppresses cell migration and establishes proper central spindle assembly for cytokinesis. Importantly, those biological effects are mediated by the inhibitory activity of LZTS2 on Katanin. LZTS2 binding to Katanin also plays a role in Katanin transport to the midbody to control proper abscis- sion. Therapeutic applications of the interaction between LZTS2 and Katanin in tumor cells are a potential area for future research. Keywords: LAPSER1 • LZTS2 • Katanin • β-catenin • Microtubule • Cancer © Versita Warsaw and Springer-Verlag Berlin Heidelberg. 1. Introduction β-tubulin cause resistance to taxanes [2]. Farnesyltransferase inhibitors, which were initially found to inhibit the Ras oncoprotein, can enhance the binding Pharmaceutical discovery has been aided by elucidation between β-tubulin and taxanes to reverse resistance to of mechanisms by which tumor suppressors inhibit taxanes [3]. The genomic region that involves Aurora-A cancer progression. For example, the discovery of is commonly amplified in human tumors with taxane taxanes as microtubule-stabilizing drugs has shown resistance. -
The Importance of Lattice Defects in Katanin-Mediated Microtubule Severing in Vitro
2916 Biophysical Journal Volume 82 June 2002 2916–2927 The Importance of Lattice Defects in Katanin-Mediated Microtubule Severing in Vitro Liza J. Davis,* David J. Odde,† Steven M. Block,‡ and Steven P. Gross§ Departments of *Chemical Engineering and Materials Science and †Biomedical Engineering, University of Minnesota, Minneapolis, Minnesota 55455; ‡Department of Biological Sciences, Stanford University, Stanford, California 94305; and §Department of Developmental and Cell Biology, University of California-Irvine, Irvine, California 92697 USA ABSTRACT The microtubule-severing enzyme katanin uses ATP hydrolysis to disrupt noncovalent bonds between tubulin dimers within the microtubule lattice. Although its microtubule severing activity is likely important for fundamental processes including mitosis and axonal outgrowth, its mechanism of action is poorly understood. To better understand this activity, an in vitro assay was developed to enable the real-time observation of katanin-mediated severing of individual, mechanically unconstrained microtubules. To interpret the experimental observations, a number of theoretical models were developed and compared quantitatively to the experimental data via Monte Carlo simulation. Models that assumed that katanin acts on a uniform microtubule lattice were incompatible with the in vitro data, whereas a model that assumed that katanin acts preferentially on spatially infrequent microtubule lattice defects was found to correctly predict the experimentally observed breaking rates, number and spatial frequency of severing events, final levels of severing, and sensitivity to katanin concen- tration over the range 6–300 nM. As a result of our analysis, we propose that defects in the microtubule lattice, which are known to exist but previously not known to have any biological function, serve as sites for katanin activity. -
Mgcracgap Controls the Assembly of the Contractile Ring and the Initiation of Cytokinesis
MgcRacGAP controls the assembly of the contractile ring and the initiation of cytokinesis Wei-meng Zhao and Guowei Fang* Department of Biological Sciences, Stanford University, Stanford, CA 94305-5020 Edited by Raymond L. Erikson, Harvard University, Cambridge, MA, and approved August 1, 2005 (received for review May 19, 2005) Initiation of cytokinesis requires the establishment of the cleavage GTPase-activating protein MgcRacGAP. Centralspindlin pro- plane, the assembly of the contractile ring, and the ingression of motes microtubule bundling in vitro and is required for cytoki- the cleavage furrow. MgcRacGAP, a GTPase-activating protein for nesis in vivo (17). However, the exact mechanism of centralspin- RhoA, is required for cytokinesis, but the mechanism of its action dlin function in cytokinesis remains to be characterized. In remains unknown. We report here that MgcRacGAP is required for Drosophila, the centralspindlin complex is reported to form a the assembly of anillin and myosin into the contractile ring. In ring-like structure that abuts or overlaps the contractile ring (13). addition, MgcRacGAP is required for the localized activation of Interestingly, RacGAP50C, the Drosophila ortholog of MgcRac- myosin through the RhoA-mediated phosphorylation of the myo- GAP, interacts with Pebble, linking the centralspindlin complex sin regulatory light chain. Cells with MgcRacGAP RNA interference to the ECT2 pathway (18). (RNAi) failed cytokinesis without any ingression of the cleavage In an in vitro small-pool-expression screen, we identified furrow. Paradoxically, MgcRacGAP, a GTPase-activating protein, MgcRacGAP as a substrate of the anaphase-promoting com- associates during cytokinesis with ECT2, a guanine nucleotide plex͞cyclosome, a ubiquitin ligase that controls mitotic progres- exchange factor for RhoA, and the localization of ECT2 to both the sion (data not shown). -
Microtubule Motors
Microtubule Forces Kevin Slep Microtubules are a Dynamic Scaffold Microtubules in red, XMA215 family MT polymerase protein in green Some Microtubule Functions Cell Structure Polarized Motor Track (kinesins and dynein) Cilia structure (motile and sensory) Mitotic and meiotic spindle structure Cell polarity Coordinate cell motility with the F-actin network Architecture of Tubulin and the Microtubule α/β-Tubulin: The Microtubule Building Block Tubulin is a heterodimer composed of α and β tubulin α and β tubulin are each approximately • 55 kD and are structurally very similar to •each other. •Each tubulin binds GTP: The α GTP is non- exchangeable and the dimer is very stable, Kd = 10-10; the β GTP is exchangeable in the dimer The Microtubule Architecture Tubulin binds head-to-tail along + protofilaments, forming LONGITUDINAL interactions. Longitudinal interactions complete the active site for GTP hydrolysis 13 protofilaments form a hollow tube-the microtubule: 25 nm OD, 14 nm ID (protofilaments interact via LATERAL interactions) The MT is a left-handed helix with a seam, it rises 1.5 heterodimers per turn (α and β form lateral interactions) MTs are polar-they have a plus end and a minus end - The γTubulin Ring Complex (γTuRC) forms a lockwasher to nucleate MTs Axial view Side View γTuRC positions nucleated 13 γTubulins in a ring γTuRC attachment microtubule The Centrosome is a Microtubule Organizing Center (MTOC) rich in γTuRC MTOC’s control where microtubules are formed Centrosomes contain peri-centrosomal material (PCM) surrounding a pair of centrioles γTuRC nucleation complexes are localized to the PCM Centrioles within centrosomes become basal bodies, which are nucleation centers for cilia (motile and primary) and flagella Centrosomes duplicate once per cell cycle Mother centriole nucleates growth of a daughter centriole with an orthogonal orientation Microtubule Polarity and Dynamics Polarized Microtubule Organization in Vivo Centrosome + + + + + + + + + Interphase Mitosis Microtubules are Dynamic Fish melanophore injected with Cy3-tubulin Vorobjev, I.A. -
Efficient Cytokinesis
Published January 23, 2006 JCB: ARTICLE <doi>10.1083/jcb.200511061</doi><aid>200511061</aid>KIF14 and citron kinase act together to promote effi cient cytokinesis Ulrike Gruneberg,1 Rüdiger Neef,2 Xiuling Li,1 Eunice H.Y. Chan,1 Ravindra B. Chalamalasetty,1 Erich A. Nigg,1 and Francis A. Barr2 1Department of Cell Biology and 2Intracellular Protein Transport Group, Max-Planck-Institute of Biochemistry, 82152 Martinsried, Germany ultiple mitotic kinesins and microtubule- EMBO J. 19:5711–5719; Matuliene, J., and R. Kuriyama. associated proteins (MAPs) act in concert to 2002. Mol. Biol. Cell. 13:1832–1845; Kurasawa, Y., W.C. M direct cytokinesis (Glotzer, M. 2005. Science. Earnshaw, Y. Mochizuki, N. Dohmae, and K. Todokoro. 307:1735–1739). In anaphase cells, many of these pro- 2004. EMBO J. 23:3237–3248). We fi nd that KIF14 tar- teins associate with an antiparallel array of microtubules gets to the central spindle via its interaction with PRC1 and Downloaded from termed the central spindle. The MAP and micro tubule- has an essential function in cytokinesis. In KIF14-depleted bundling protein PRC1 (protein-regulating cytokinesis 1) cells, citron kinase but not other components of the central is one of the key molecules required for the integrity of spindle and cleavage furrow fail to localize. Furthermore, this structure (Jiang, W., G. Jimenez, N.J. Wells, T.J. Hope, the localization of KIF14 and citron kinase to the central G.M. Wahl, T. Hunter, and R. Fukunaga. 1998. Mol. spindle and midbody is codependent, and they form a com- Cell. 2:877–885; Mollinari, C., J.P. -
Determination of the Cleavage Plane in Early C. Elegans Embryos
ANRV361-GE42-18 ARI 11 October 2008 11:24 ANNUAL Determination of the REVIEWS Further Click here for quick links to Annual Reviews content online, Cleavage Plane in Early including: • Other articles in this volume Embryos • Top cited articles C. elegans • Top downloaded articles • Our comprehensive search Matilde Galli and Sander van den Heuvel Developmental Biology, Utrecht University, 3584 CH Utrecht, The Netherlands; email: [email protected] Annu. Rev. Genet. 2008. 42:389–411 Key Words First published online as a Review in Advance on cytokinesis, cleavage plane, asymmetric division, spindle positioning, August 18, 2008 C. elegans The Annual Review of Genetics is online at genet.annualreviews.org Abstract This article’s doi: Cells split in two at the final step of each division cycle. This division 10.1146/annurev.genet.40.110405.090523 Access provided by Utrecht University on 12/02/17. For personal use only. normally bisects through the middle of the cell and generates two equal Annu. Rev. Genet. 2008.42:389-411. Downloaded from www.annualreviews.org Copyright c 2008 by Annual Reviews. daughters. However, developmental signals can change the plane of cell All rights reserved cleavage to facilitate asymmetric segregation of fate determinants and 0066-4197/08/1201-0389$20.00 control the position and relative sizes of daughter cells. The anaphase spindle instructs the site of cell cleavage in animal cells, hence its po- sition is critical in the regulation of symmetric vs asymmetric cell divi- sion. Studies in a variety of models identified evolutionarily conserved mechanisms that control spindle positioning. -
The Mitotic Tensegrity Guardian Tau Protects Mammary Epithelia from Katanin-Like1-Induced Aneuploidy
www.impactjournals.com/oncotarget/ Oncotarget, Vol. 7, No. 33 Research Paper The mitotic tensegrity guardian tau protects mammary epithelia from katanin-like1-induced aneuploidy Haruka Sudo1,2, Kazunori Nakajima2 1Department of Biochemistry, The Nippon Dental University School of Life Dentistry at Tokyo, 1-9-20 Fujimi, Chiyoda-ku, Tokyo 102-8159, Japan 2Department of Anatomy, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan Correspondence to: Haruka Sudo, email: [email protected] Keywords: breast cancer, chromosome instability, microtubule severing, mitotic spindle, tau Received: January 17, 2016 Accepted: June 16, 2016 Published: July 20, 2016 ABSTRACT The microtubule associated-protein tau has been identified as an effective positive prognostic indicator in breast cancer. To explore the physiological function of tau in early carcinogenesis, endogenous tau was knocked down in primary cultured human mammary epithelial cells. This resulted in chromosome-bridging during anaphase followed by micronucleation, both of which were suppressed by a further katanin- like1 knockdown. We also detected that the exogenously expressed katanin-like1 induction of cellular transformation is prevented by exogenous tau in rat fibroblasts. The mutant katanin-like1 (L123V) identified in breast cancer showed an increase in this transformation capacity as well as microtubule severing activity resistant to tau. The tau knockdown resulted in a loss of the kinetochore fibers on which tau is normally localized. This physical fragility was also observed in isolated tau- knockdown mitotic spindles, supporting the relevance of microtubule damage to the onset of transformation. The karyotyping of tau-knockdown cells showed increased frequency of loss of one X chromosome, further suggesting the involvement of tau in breast tumorigenesis. -
Spindle Assembly and Chromosome Segregation Requires Central Spindle Proteins in Drosophila Oocytes
HIGHLIGHTED ARTICLE | INVESTIGATION Spindle Assembly and Chromosome Segregation Requires Central Spindle Proteins in Drosophila Oocytes Arunika Das,* Shital J. Shah,* Bensen Fan,* Daniel Paik,* Daniel J. DiSanto,* Anna Maria Hinman,* Jeffry M. Cesario,* Rachel A. Battaglia,* Nicole Demos,* and Kim S. McKim*,†,1 *Waksman Institute, Rutgers, The State University of New Jersey, New Jersey 08854, and †Department of Genetics, Rutgers, The State University of New Jersey, New Jersey 08854 ABSTRACT Oocytes segregate chromosomes in the absence of centrosomes. In this situation, the chromosomes direct spindle assembly. It is still unclear in this system which factors are required for homologous chromosome bi-orientation and spindle assembly. The Drosophila kinesin-6 protein Subito, although nonessential for mitotic spindle assembly, is required to organize a bipolar meiotic spindle and chromosome bi-orientation in oocytes. Along with the chromosomal passenger complex (CPC), Subito is an important part of the metaphase I central spindle. In this study we have conducted genetic screens to identify genes that interact with subito or the CPC component Incenp. In addition, the meiotic mutant phenotype for some of the genes identified in these screens were charac- terized. We show, in part through the use of a heat-shock-inducible system, that the Centralspindlin component RacGAP50C and downstream regulators of cytokinesis Rho1, Sticky, and RhoGEF2 are required for homologous chromosome bi-orientation in meta- phase I oocytes. This suggests a novel function for proteins normally involved in mitotic cell division in the regulation of microtubule– chromosome interactions. We also show that the kinetochore protein, Polo kinase, is required for maintaining chromosome alignment and spindle organization in metaphase I oocytes. -
Terms Moving from Supplemental Concepts to Descriptor Records (Promotions)
Terms Moving From Supplemental Concepts to Descriptor Records (Promotions) Term Type EntryTerm Moved 2017 UI 2017 Heading Moved To 2018 MeSH UI 2018 Heading From Entry Tem ATPase, Cu++ transporting, beta polypeptide (Wilson SCR C093154 Wilson disease protein Descriptor D000073840 Copper-transporting ATPases disease) Entry Tem DNA-binding protein CTCF SCR C109778 CCCTC-binding factor Descriptor D000076246 CCCTC-Binding Factor Entry Tem valosine-containing protein SCR C070098 CDC48 protein Descriptor D000074405 Valosin Containing Protein Heading COP9 signalosome complex SCR C088436 COP9 signalosome complex Descriptor D000075686 COP9 Signalosome Complex Entry Tem Campath 1M SCR C096529 alemtuzumab Descriptor D000074323 Alemtuzumab Entry Tem guanyl cyclase-C receptor SCR C032215 enterotoxin receptor Descriptor D000074261 Receptors, Enterotoxin Entry Tem valosin-containing protein SCR C070098 CDC48 protein Descriptor D000074405 Valosin Containing Protein Entry Tem monoclonal antibody Campath-1H SCR C096529 alemtuzumab Descriptor D000074323 Alemtuzumab Heading netrin-1 SCR C088893 netrin-1 Descriptor D000075388 Netrin-1 Heading C.I. Acid Red 27 SCR C493143 C.I. -
Augmin-Mediated Amplification of Long-Lived Spindle Microtubules Directs Plus-Ends to Kinetochores
bioRxiv preprint doi: https://doi.org/10.1101/501445; this version posted December 19, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Augmin-mediated amplification of long-lived spindle microtubules directs plus-ends to kinetochores Authors: Ana F. David1, Philippe Roudot2, Wesley R. Legant3, 4, Eric Betzig3, Gaudenz Danuser2, and Daniel W. Gerlich1* Affiliations: 1Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter (VBC), 1030 Vienna, Austria. 2Department oF Cell Biology and Lyda Hill Department oF BioinFormatics, University oF Texas Southwestern Medical Center, Dallas, USA. 3Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, USA. 4Present address: Department oF Biomedical Engineering, Department oF Pharmacology, University oF North Carolina Chapel Hill, Chapel Hill, USA. *Correspondence to D.W.G., ORCID 0000-0003-1637-3365, Email: [email protected] Dividing cells reorganize their microtubule cytoskeleton into a bipolar spindle, which moves one set of sister chromatids to each nascent daughter cell. Early spindle assembly models postulated that spindle-pole-derived microtubules search the cytoplasmic space until they randomly encounter a kinetochore to form a stable attachment. More recent work uncovered several additional, centrosome-independent microtubule generation pathways, but the contributions of each pathway to spindle assembly have remained unclear. Here, we combined live microscopy and mathematical modeling to show that most microtubules nucleate at non-centrosomal regions in dividing human cells.