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PMID: 12837247 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Human CLASP1 is an outer kinetochore component that regulates spindle microtubule dynamics.

Cell ·Vol. 113 ·No. 7 ·2003-06-27 ·Pages 891-904

Maiato H, Fairley EA, Rieder CL, Swedlow JR, Sunkel CE, Earnshaw WC

Abstract

One of the most intriguing aspects of mitosis is the ability of kinetochores to hold onto plus ends of microtubules that are actively gaining or losing tubulin subunits. Here, we show that CLASP1, a microtubule-associated protein, localizes preferentially near the plus ends of growing spindle microtubules and is also a component of a kinetochore region that we term the outer corona. A truncated form of CLASP1 lacking the kinetochore binding domain behaves as a dominant negative, leading to the formation of radial arrays of microtubule bundles that are highly resistant to depolymerization. Microinjection of CLASP1-specific antibodies suppresses microtubule dynamics at kinetochores and throughout the spindle, resulting in the formation of monopolar asters with chromosomes buried in the interior. Incubation with microtubule-stabilizing drugs rescues the kinetochore association with microtubule plus ends at the periphery of the asters. Our data suggest that CLASP1 is required at kinetochores for attached microtubules to exhibit normal dynamic behavior.

MeSH Terms
Antibodies Eukaryotic Cells/metabolism,ultrastructure HeLa Cells Humans Kinetochores/metabolism,ultrastructure Microscopy, Electron Microtubule-Associated Proteins/antagonists & inhibitors,genetics,metabolism Microtubules/metabolism,ultrastructure Mitosis/genetics Mutation/genetics Nuclear Proteins/genetics,metabolism Phenotype Protein Structure, Tertiary/genetics Recombinant Fusion Proteins Spindle Apparatus/metabolism,ultrastructure
Chemicals
Antibodies Clasp protein, mouse Microtubule-Associated Proteins Nuclear Proteins Recombinant Fusion Proteins
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Maiato Helder
Chromosome Structure Group, Wellcome Trust Centre for Cell Biology, Institute of Cell and Molecular Biology, University of Edinburgh, Swann Building, King's Buildings, Mayfield Road, EH9 3JR, Scotland, Edinburgh, United Kingdom.
Fairley Elizabeth A L
Rieder Conly L
Swedlow Jason R
Sunkel Claudio E
Earnshaw William C
Article Info
Journal
Cell
Abbr.
Cell
ISSN
0092-8674
Published
2003-06-27
Pages
891-904
Language
English
Region
United States
NLM ID
0413066
Subset
IM
Grants
Wellcome Trust · 073915 · United Kingdom
NIGMS NIH HHS · R37 GM040198 · United States
NIGMS NIH HHS · R37 GM040198-20 · United States
NIGMS NIH HHS · GM 40198 · United States
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