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Vol. 18, Issue 7, 2656-2666, July 2007

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Nudel Modulates Kinetochore Association and Function of Cytoplasmic Dynein in M Phase

Yun Liang^*,, Wei Yu^*,, Yan Li^*,, Lihou Yu^*, Qiangge Zhang^*, Fubin Wang^*, Zhenye Yang^*, Juan Du^*, Qiongping Huang^*, Xuebiao Yao, and Xueliang Zhu^*

*Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; and Hefei National Laboratory for Physical Sciences and the School of Life Sciences, University of Science and Technology of China, Anhui 230027, China

Submitted April 26, 2006; Revised March 22, 2007; Accepted April 26, 2007
Monitoring Editor: Kerry Bloom

The microtubule-based motor cytoplasmic dynein/dynactin is a force generator at the kinetochore. It also transports proteins away from kinetochores to spindle poles. Regulation of such diverse functions, however, is poorly understood. We have previously shown that Nudel is critical for dynein-mediated protein transport, whereas mitosin, a kinetochore protein that binds Nudel, is involved in retention of kinetochore dynein/dynactin against microtubule-dependent stripping. Here we demonstrate that Nudel is required for robust localization of dynein/dynactin at the kinetochore. It localizes to kinetochores after nuclear envelope breakdown, depending mostly (78%) on mitosin and slightly on dynein/dynactin. Depletion of Nudel by RNA interference (RNAi) or overexpression of its mutant incapable of binding either Lis1 or dynein heavy chain abolishes the kinetochore protein transport and mitotic progression. Similar to mitosin RNAi, Nudel RNAi also leads to increased stripping of kinetochore dynein/dynactin in the presence of microtubules. Taking together, our results suggest a dual role of kinetochore Nudel: it activates dynein-mediated protein transport and, when interacting with both mitosin and dynein, stabilizes kinetochore dynein/dynactin against microtubule-dependent stripping to facilitate the force generation function of the motor.

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

These authors contributed equally to this work.

Address correspondence to: Xueliang Zhu (xlzhu{at}sibs.ac.cn)

Abbreviations used: DHC, dynein heavy chain; DIC, dynein intermediate chain; GFP, green fluorescence protein; MT, microtubule; NEBD, nuclear envelope breakdown; RFP, red fluorescence protein; RNAi, RNA interference.

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