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MAP4 and CLASP1 operate as a safety mechanism to maintain a stable spindle position in mitosis

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Samora, Catarina P., Mogessie, Binyam, Conway, Leslie, Ross, Jennifer L., Straube, Anne and McAinsh, Andrew D.. (2011) MAP4 and CLASP1 operate as a safety mechanism to maintain a stable spindle position in mitosis. Nature Cell Biology, Vol.13 (No.9). pp. 1040-1050. ISSN 1465-7392

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Official URL: http://dx.doi.org/10.1038/ncb2297

Abstract

Correct positioning of the mitotic spindle is critical to establish the correct cell-division plane. Spindle positioning involves capture of astral microtubules and generation of pushing/pulling forces at the cell cortex. Here we show that the tau-related protein MAP4 and the microtubule rescue factor CLASP1 are essential for maintaining spindle position and the correct cell-division axis in human cells. We propose that CLASP1 is required to correctly capture astral microtubules, whereas MAP4 prevents engagement of excess dynein motors, thereby protecting the system from force imbalance. Consistent with this, MAP4 physically interacts with dynein–dynactin in vivo and inhibits dynein-mediated microtubule sliding in vitro. Depletion of MAP4, but not CLASP1, causes spindle misorientation in the vertical plane, demonstrating that force generators are under spatial control. These findings have wide biological importance, because spindle positioning is essential during embryogenesis and stem-cell homeostasis.

Item Type: Journal Article
Subjects: Q Science > QH Natural history > QH301 Biology
Q Science > QH Natural history > QH426 Genetics
Divisions: Faculty of Science > Life Sciences (2010- )
Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH): Mitosis, Microtubules, Spindle (Cell division)
Journal or Publication Title: Nature Cell Biology
Publisher: Nature Publishing Group
ISSN: 1465-7392
Date: September 2011
Volume: Vol.13
Number: No.9
Page Range: pp. 1040-1050
Identification Number: 10.1038/ncb2297
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access
Funder: Marie Curie Cancer Care, National Science Foundation (U.S.) (NSF)
Grant number: DGE-0654128 (NSF)
URI: http://wrap.warwick.ac.uk/id/eprint/36914

Data sourced from Thomson Reuters' Web of Knowledge

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