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J Cell Biol. 2009 Jun 1;185(5):859-74. doi: 10.1083/jcb.200812167. Epub 2009 May 25.

Mitotic control of kinetochore-associated dynein and spindle orientation by human Spindly.

Author information

1
Department of Cell Biology, Max Planck Institute of Biochemistry, D-82152 Martinsried, Germany.

Abstract

Mitotic spindle formation and chromosome segregation depend critically on kinetochore-microtubule (KT-MT) interactions. A new protein, termed Spindly in Drosophila and SPDL-1 in C. elegans, was recently shown to regulate KT localization of dynein, but depletion phenotypes revealed striking differences, suggesting evolutionarily diverse roles of mitotic dynein. By characterizing the function of Spindly in human cells, we identify specific functions for KT dynein. We show that localization of human Spindly (hSpindly) to KTs is controlled by the Rod/Zw10/Zwilch (RZZ) complex and Aurora B. hSpindly depletion results in reduced inter-KT tension, unstable KT fibers, an extensive prometaphase delay, and severe chromosome misalignment. Moreover, depletion of hSpindly induces a striking spindle rotation, which can be rescued by co-depletion of dynein. However, in contrast to Drosophila, hSpindly depletion does not abolish the removal of MAD2 and ZW10 from KTs. Collectively, our data reveal hSpindly-mediated dynein functions and highlight a critical role of KT dynein in spindle orientation.

PMID:
19468067
PMCID:
PMC2711594
DOI:
10.1083/jcb.200812167
[Indexed for MEDLINE]
Free PMC Article

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