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Published 17 February 2004. doi:10.1083/jcb.200308058
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 164, Number 4, 557-566
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Article

Nudel functions in membrane traffic mainly through association with Lis1 and cytoplasmic dynein

Yun Liang, Wei Yu, Yan Li, Zhenye Yang, Xiumin Yan, Qiongping Huang, 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

Address correspondence to Xueliang Zhu, Institute of Biochemistry and Cell Biology, 320 Yue Yang Rd., Shanghai 200031, China. Tel.: 86-21-54921406. Fax: 86-21-54921011. email: xlzhu{at}sibs.ac.cn

Nudel and Lis1 appear to regulate cytoplasmic dynein in neuronal migration and mitosis through direct interactions. However, whether or not they regulate other functions of dynein remains elusive. Herein, overexpression of a Nudel mutant defective in association with either Lis1 or dynein heavy chain is shown to cause dispersions of membranous organelles whose trafficking depends on dynein. In contrast, the wild-type Nudel and the double mutant that binds to neither protein are much less effective. Time-lapse microscopy for lysosomes reveals significant reduction in both frequencies and velocities of their minus end–directed motions in cells expressing the dynein-binding defective mutant, whereas neither the durations of movement nor the plus end–directed motility is considerably altered. Moreover, silencing Nudel expression by RNA interference results in Golgi apparatus fragmentation and cell death. Together, it is concluded that Nudel is critical for dynein motor activity in membrane transport and possibly other cellular activities through interactions with both Lis1 and dynein heavy chain.

Key Words: NudE; organelle; motility; time-lapse microscopy; RNA interference


Y. Liang and W. Yu contributed equally to this work.

The online version of this article includes supplemental material.

Abbreviations used in this paper: DHC, dynein heavy chain; DIC, dynein intermediate chain; ERGIC, ER-to-Golgi intermediate compartment; hPL, human placental lactogen; MT, microtubule; RNAi, RNA interference; SiRNA, small interference RNA; Tet, tetracycline.


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