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, Xueliang Zhu

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72 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2656-2666
Number of pages11
JournalMolecular biology of the cell
Volume18
Issue number7
DOIs
StatePublished - Jul 2007
Externally publishedYes

ASJC Scopus subject areas

  • General Medicine

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