Myosin V spatially regulates microtubule dynamics and promotes the ubiquitin-dependent degradation of the fission yeast CLIP-170 homologue, Tip1

Coordination between microtubule and actin cytoskeletons plays a crucial role during the establishment of cell polarity. In fission yeast, the microtubule cytoskeleton regulates the distribution of actin assembly at the new growing end during the monopolar-to-bipolar growth transition. Here, we describe a novel mechanism in which a myosin V modulates the spatial coordination of proteolysis and microtubule dynamics. In cells lacking a functional copy of the class V myosin, Myo52, the plus ends of microtubules fail to undergo catastrophe on contacting the cell end and continue to grow, curling around the end of the cell. We show that this actin-associated motor regulates the efficient ubiquitin-dependent proteolysis of the Schizosaccharomyces pombe CLIP-170 homologue, Tip1. Myo52 facilitates microtubule catastrophe by enhancing Tip1 removal from the plus end of growing microtubules at the cell tips. There, Myo52 and the ubiquitin receptor, Dph1, work in concert to target Tip1 for degradation.

[1]  Tobias A. Knoch,et al.  Dynamic behavior of GFP–CLIP-170 reveals fast protein turnover on microtubule plus ends , 2008, The Journal of cell biology.

[2]  S. Bratman,et al.  Stabilization of overlapping microtubules by fission yeast CLASP. , 2007, Developmental cell.

[3]  Daniel P. Mulvihill,et al.  In vivo movement of the type V myosin Myo52 requires dimerisation but is independent of the neck domain , 2007, Journal of Cell Science.

[4]  T. Natsume,et al.  Wnt signalling regulates paxillin ubiquitination essential for mesodermal cell motility , 2007, Nature Cell Biology.

[5]  J. Boettcher,et al.  Ubiquitin-dependent proteolysis of the microtubule end-binding protein 1, EB1, is controlled by the COP9 signalosome: possible consequences for microtubule filament stability. , 2007, Journal of molecular biology.

[6]  D. Manstein,et al.  Functional Characterization of the N-terminal Region of Myosin-2* , 2006, Journal of Biological Chemistry.

[7]  H. Rockoff On the Origins of , 2006 .

[8]  S. Bagley,et al.  S. pombe CLASP needs dynein, not EB1 or CLIP170, to induce microtubule instability and slows polymerization rates at cell tips in a dynein-dependent manner. , 2006, Genes & development.

[9]  D. J. Clarke,et al.  UBL/UBA ubiquitin receptor proteins bind a common tetraubiquitin chain. , 2006, Journal of molecular biology.

[10]  Daniel P. Mulvihill,et al.  A critical role for the type V myosin, Myo52, in septum deposition and cell fission during cytokinesis in Schizosaccharomyces pombe. , 2006, Cell motility and the cytoskeleton.

[11]  J. Hammer,et al.  Melanophilin and myosin Va track the microtubule plus end on EB1 , 2005, The Journal of cell biology.

[12]  S. Elsasser,et al.  Delivery of ubiquitinated substrates to protein-unfolding machines , 2005, Nature Cell Biology.

[13]  S. Uzawa,et al.  Wsh3/Tea4 Is a Novel Cell-End Factor Essential for Bipolar Distribution of Tea1 and Protects Cell Polarity under Environmental Stress in S. pombe , 2005, Current Biology.

[14]  P. Nurse,et al.  The nuclear rim protein Amo1 is required for proper microtubule cytoskeleton organisation in fission yeast , 2005, Journal of Cell Science.

[15]  Sophie G. Martin,et al.  Tea4p links microtubule plus ends with the formin for3p in the establishment of cell polarity. , 2005, Developmental cell.

[16]  M. Chen,et al.  EB1 and APC bind to mDia to stabilize microtubules downstream of Rho and promote cell migration , 2004, Nature Cell Biology.

[17]  K. E. Busch,et al.  The Microtubule Plus End-Tracking Proteins mal3p and tip1p Cooperate for Cell-End Targeting of Interphase Microtubules , 2004, Current Biology.

[18]  S. Reed,et al.  Ratchets and clocks: the cell cycle, ubiquitylation and protein turnover , 2003, Nature Reviews Molecular Cell Biology.

[19]  Steven P Gygi,et al.  A subset of membrane-associated proteins is ubiquitinated in response to mutations in the endoplasmic reticulum degradation machinery , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[20]  Y. Barral,et al.  Spindle orientation in Saccharomyces cerevisiae depends on the transport of microtubule ends along polarized actin cables , 2003, The Journal of cell biology.

[21]  D. Glover,et al.  A ‘marker switch’ approach for targeted mutagenesis of genes in Schizosaccharomyces pombe , 2003, Yeast.

[22]  Tetsu Akiyama,et al.  Mutated APC and Asef are involved in the migration of colorectal tumour cells , 2003, Nature Cell Biology.

[23]  R. Hartmann-Petersen,et al.  Ubiquitin binding proteins protect ubiquitin conjugates from disassembly , 2003, FEBS letters.

[24]  L. Serpell,et al.  Proteasomal degradation of tau protein , 2002, Journal of neurochemistry.

[25]  S. Kuroda,et al.  Rac1 and Cdc42 Capture Microtubules through IQGAP1 and CLIP-170 , 2002, Cell.

[26]  Hai Rao,et al.  Recognition of Specific Ubiquitin Conjugates Is Important for the Proteolytic Functions of the Ubiquitin-associated Domain Proteins Dsk2 and Rad23* , 2002, The Journal of Biological Chemistry.

[27]  Colin Gordon,et al.  Proteins containing the UBA domain are able to bind to multi-ubiquitin chains , 2001, Nature Cell Biology.

[28]  Jacqueline Hayles,et al.  A journey into space , 2001, Nature Reviews Molecular Cell Biology.

[29]  I. Mabuchi,et al.  Identification of two type V myosins in fission yeast, one of which functions in polarized cell growth and moves rapidly in the cell. , 2001, Molecular biology of the cell.

[30]  J. McIntosh,et al.  Tea2p Is a Kinesin-like Protein Required to Generate Polarized Growth in Fission Yeast , 2000, The Journal of cell biology.

[31]  P. Nurse,et al.  CLIP170-like tip1p Spatially Organizes Microtubular Dynamics in Fission Yeast , 2000, Cell.

[32]  Anthony Bretscher,et al.  Myosin V orientates the mitotic spindle in yeast , 2000, Nature.

[33]  D. Drubin,et al.  Functional cooperation between the microtubule and actin cytoskeletons. , 2000, Current opinion in cell biology.

[34]  Matthias Rief,et al.  Myosin-V is a processive actin-based motor , 1999, Nature.

[35]  J. McIntosh,et al.  Localization of the 26S proteasome during mitosis and meiosis in fission yeast , 1998, The EMBO journal.

[36]  P. Nurse,et al.  Regulation of Cell Polarity by Microtubules in Fission Yeast , 1998, The Journal of cell biology.

[37]  P. Philippsen,et al.  Heterologous modules for efficient and versatile PCR‐based gene targeting in Schizosaccharomyces pombe , 1998, Yeast.

[38]  M. Jones,et al.  Mph1, a member of the Mps1-like family of dual specificity protein kinases, is required for the spindle checkpoint in S. pombe. , 1998, Journal of cell science.

[39]  M. Balasubramanian,et al.  Rng2p, a protein required for cytokinesis in fission yeast, is a component of the actomyosin ring and the spindle pole body , 1998, Current Biology.

[40]  K. Miller,et al.  A Class VI Unconventional Myosin Is Associated with a Homologue of a Microtubule-binding Protein, Cytoplasmic Linker Protein–170, in Neurons and at the Posterior Pole of Drosophila Embryos , 1998, The Journal of cell biology.

[41]  J. Benito,et al.  Regulation of the G1 phase of the cell cycle by periodic stabilization and degradation of the p25rum1 CDK inhibitor , 1998, The EMBO journal.

[42]  J. Hegemann,et al.  Mal3, the Fission Yeast Homologue of the Human APC-interacting Protein EB-1 Is Required for Microtubule Integrity and the Maintenance of Cell Form , 1997, The Journal of cell biology.

[43]  P. Nurse,et al.  tea1 and the Microtubular Cytoskeleton Are Important for Generating Global Spatial Order within the Fission Yeast Cell , 1997, Cell.

[44]  C. Gordon,et al.  A Conditional Lethal Mutant in the Fission Yeast 26 S Protease Subunit mts3 Is Defective in Metaphase to Anaphase Transition (*) , 1996, The Journal of Biological Chemistry.

[45]  D. Drubin,et al.  Origins of Cell Polarity , 1996, Cell.

[46]  P. Nurse,et al.  Fission yeast cell morphogenesis: identification of new genes and analysis of their role during the cell cycle , 1995, The Journal of cell biology.

[47]  T. Kreis,et al.  Binding of pp170 to microtubules is regulated by phosphorylation. , 1991, The Journal of biological chemistry.

[48]  I. Hagan,et al.  The use of cell division cycle mutants to investigate the control of microtubule distribution in the fission yeast Schizosaccharomyces pombe. , 1988, Journal of cell science.

[49]  P. Nurse,et al.  The cell cycle control gene cdc2 + of fission yeast encodes a protein kinase potentially regulated by phosphorylation , 1986, Cell.

[50]  J. Marks,et al.  Growth Polarity and Cytokinesis in Fission Yeast: The Role of the Cytoskeleton , 1986, Journal of Cell Science.

[51]  P. Nurse,et al.  Growth in cell length in the fission yeast Schizosaccharomyces pombe. , 1985, Journal of cell science.

[52]  A. Zurn,et al.  The cytoskeleton and specification of neuronal morphology. , 1981, Neurosciences Research Program bulletin.

[53]  W. Crocker,et al.  Polarity , 1910, Botanical Gazette.

[54]  S. Reed The ubiquitin-proteasome pathway in cell cycle control. , 2006, Results and problems in cell differentiation.

[55]  F. Chang,et al.  Effects of {gamma}-tubulin complex proteins on microtubule nucleation and catastrophe in fission yeast. , 2005, Molecular biology of the cell.

[56]  R. Hartmann-Petersen,et al.  Transferring substrates to the 26S proteasome. , 2003, Trends in biochemical sciences.

[57]  Daniel P. Mulvihill,et al.  Two type V myosins with non-overlapping functions in the fission yeast Schizosaccharomyces pombe: Myo52 is concerned with growth polarity and cytokinesis, Myo51 is a component of the cytokinetic actin ring. , 2001, Journal of cell science.

[58]  S. Moreno,et al.  Molecular genetic analysis of fission yeast Schizosaccharomyces pombe. , 1991, Methods in enzymology.