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J. Biol. Chem., Vol. 283, Issue 18, 12232-12240, May 2, 2008

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 283/18/12232    most recent M710200200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Shim, S. Y. Articles by Nguyen, M. D. PubMed PubMed Citation Articles by Shim, S. Y. Articles by Nguyen, M. D. Social Bookmarking                      What's this?

Ndel1 Controls the Dynein-mediated Transport of Vimentin during Neurite Outgrowth^*

Su Yeon Shim^¶, Benjamin Adam Samuels^||1, Jian Wang^¶1, Gernot Neumayer^¶, Camille Belzil^¶, Ramses Ayala^||, Yang Shi^**, Yujiang Shi^**, Li-Huei Tsai^||, and Minh Dang Nguyen^¶2

From the Departments of Clinical Neurosciences, Cell Biology and Anatomy, and ^¶Biochemistry and Molecular Biology, Hotchkiss Brain Institute, University of Calgary, Calgary T2N 4N1, Canada, the ^||Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Boston, Massachusetts 02139, and the ^**Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115

Ndel1, the mammalian homologue of the Aspergillus nidulans NudE, is emergently viewed as an integrator of the cytoskeleton. By regulating the dynamics of microtubules and assembly of neuronal intermediate filaments (IFs), Ndel1 promotes neurite outgrowth, neuronal migration, and cell integrity (1–6). To further understand the roles of Ndel1 in cytoskeletal dynamics, we performed a tandem affinity purification of Ndel1-interacting proteins. We isolated a novel Ndel1 molecular complex composed of the IF vimentin, the molecular motor dynein, the lissencephaly protein Lis1, and the cis-Golgi-associated protein COP. Ndel1 promotes the interaction between Lis1, COP, and the vimentin-dynein complex. The functional result of this complex is activation of dynein-mediated transport of vimentin. A loss of Ndel1 functions by RNA interference fails to incorporate Lis1/COP in the complex, reduces the transport of vimentin, and culminates in IF accumulations and altered neuritogenesis. Our findings reveal a novel regulatory mechanism of vimentin transport during neurite extension that may have implications in diseases featuring transport/trafficking defects and impaired regeneration.

Received for publication, December 14, 2007 , and in revised form, February 7, 2008.

^* This work was supported in part by the Howard Hughes Medical Institute (to L.-H. T.), the amyotrophic lateral sclerosis societies of Canada/USA (to M. D. N.), the Multiple Sclerosis Society of Canada (to M. D. N.), and the Canadian Institutes of Health Research (CIHR) (to M. D. N.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement"in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1 and S2 and two movies.

¹ Both authors contributed equally to this work.

² Holds a Career Development Award from the Human Frontier Science Program Organization, a New Investigator Award from the CIHR, a scholarship from the Alberta Heritage Foundation for Medical Research, and the Brenda Strafford Foundation Chair in Alzheimer research. To whom correspondence should be addressed: Dept. of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, 3330 Hospital Drive NW, Heritage Medical Research Bldg, Room 151, Calgary T2N 4N1, Canada. Tel.: 403-210-5494; Fax: 403-210-8840; E-mail: mdnguyen{at}ucalgary.ca.

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