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Cytoskeleton (Hoboken). 2010 Nov;67(11):715-28. doi: 10.1002/cm.20482.

Coupling between microtubule sliding, plus-end growth and spindle length revealed by kinesin-8 depletion.

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1
Department of Molecular and Cell Biology, One Shields Avenue, University of California Davis, Davis, California 95616, USA.

Abstract

Mitotic spindle length control requires coordination between microtubule (MT) dynamics and motor-generated forces. To investigate how MT plus-end polymerization contributes to spindle length in Drosophila embryos, we studied the dynamics of the MT plus-end depolymerase, kinesin-8, and the effects of kinesin-8 inhibition using mutants and antibody microinjection. As expected, kinesin-8 was found to contribute to anaphase A. Furthermore, kinesin-8 depletion caused: (i) excessive polymerization of interpolar (ip) MT plus ends, which "overgrow" to penetrate distal half spindles; (ii) an increase in the poleward ipMT sliding rate that is coupled to MT plus-end polymerization; (iii) premature spindle elongation during metaphase/anaphase A; and (iv) an increase in the anaphase B spindle elongation rate which correlates linearly with the MT sliding rate. This is best explained by a revised "ipMT sliding/minus-end depolymerization" model for spindle length control which incorporates a coupling between ipMT plus end dynamics and the outward ipMT sliding that drives poleward flux and spindle elongation.

PMID:
20814910
PMCID:
PMC2998535
DOI:
10.1002/cm.20482
[Indexed for MEDLINE]
Free PMC Article
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