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Published online
doi:10.1083/jcb.200812167
The Journal of Cell Biology, Vol. 185, No. 5, 859-874
The Rockefeller University Press, 0021-9525 $30.00
© Chan et al.
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Article

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



Ying Wai Chan1, Luca L. Fava1, Andreas Uldschmid1, Michael H.A. Schmitz2, Daniel W. Gerlich2, Erich A. Nigg1,3, and Anna Santamaria1

1 Department of Cell Biology, Max Planck Institute of Biochemistry, D-82152 Martinsried, Germany
2 Institute of Biochemistry, ETHZ, CH-8093 Zürich, Switzerland
3 Biozentrum, University of Basel, CH-4056 Basel, Switzerland

Correspondence to Anna Santamaria: santamaria{at}biochem.mpg.de

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.

A. Uldschmid's present address is Viramed Biotech AG, Behingerstrasse 11, D-82152, Planegg, Germany.

Abbreviations used in this paper: DHC, dynein heavy chain; DIC, dynein intermediate chain; GL2, Photinus pyralis luciferase gene; hSpindly, human Spindly; KT, kinetochore; MT, microtubule; RZZ, Rod/Zw10/Zwilch; SAC, spindle assembly checkpoint.

© 2009 Chan et al.
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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