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PMID: 21079246 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Mitotic spindle disassembly occurs via distinct subprocesses driven by the anaphase-promoting complex, Aurora B kinase, and kinesin-8.

The Journal of cell biology ·Vol. 191 ·No. 4 ·2010-11-15 ·Pages 795-808

Woodruff JB, Drubin DG, Barnes G

Abstract

The mitotic spindle is a complex and dynamic structure. Although much has been learned about how spindles assemble and mediate chromosome segregation, how spindles rapidly and irreversibly disassemble during telophase is less clear. We used synthetic lethal screens in budding yeast to identify mutants defective in spindle disassembly. Real-time, live cell imaging analysis of spindle disassembly was performed on nine mutants defective in this process. Results of this analysis suggest that spindle disassembly is achieved by mechanistically distinct but functionally overlapping subprocesses: disengagement of the spindle halves, arrest of spindle elongation, and initiation of interpolar microtubule depolymerization. These subprocesses are largely governed by the anaphase-promoting complex, Aurora B kinase, and kinesin-8. Combinatorial inhibition of these subprocesses yielded cells with hyperstable spindle remnants and dramatic defects in cell cycle progression, establishing that rapid spindle disassembly is crucial for cell proliferation.

MeSH Terms
Anaphase-Promoting Complex-Cyclosome Aurora Kinases Cell Cycle Proteins/genetics,metabolism Cytokinesis/physiology Intracellular Signaling Peptides and Proteins/genetics,metabolism Kinesins/genetics,metabolism Microtubule Proteins/genetics,metabolism Microtubules/metabolism Myosin Heavy Chains/genetics,metabolism Myosin Type V/genetics,metabolism Protein Serine-Threonine Kinases/genetics,metabolism Recombinant Fusion Proteins/genetics,metabolism Saccharomyces cerevisiae/cytology,genetics,metabolism Saccharomyces cerevisiae Proteins/genetics,metabolism Spindle Apparatus/metabolism Tubulin/genetics,metabolism Ubiquitin-Protein Ligase Complexes/genetics,metabolism
Chemicals
BIM1 protein, S cerevisiae Cell Cycle Proteins Intracellular Signaling Peptides and Proteins KIP3 protein, S cerevisiae Microtubule Proteins Myo4 protein, S cerevisiae Recombinant Fusion Proteins Saccharomyces cerevisiae Proteins Tubulin Ubiquitin-Protein Ligase Complexes Anaphase-Promoting Complex-Cyclosome Aurora Kinases IPL1 protein, S cerevisiae Protein Serine-Threonine Kinases Myosin Type V Myosin Heavy Chains Kinesins
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Woodruff Jeffrey B
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Drubin David G
Barnes Georjana
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
1540-8140
DOI
10.1083/jcb.201006028
Published
2010-11-15
Pages
795-808
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2983061
Subset
IM
Grants
NIGMS NIH HHS · R01 GM047842 · United States
NIGMS NIH HHS · GM47842 · United States
Corrections
CommentIn
PMID: 21179056
External Links
PubMed source DOI: 10.1083/jcb.201006028 PMC Full Text View journal details
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