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Molecular and Cellular Biology, May 2002, p. 3089-3102, Vol. 22, No. 9
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.9.3089-3102.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

LIS1, CLIP-170's Key to the Dynein/Dynactin Pathway

Frédéric M. Coquelle,1 Michal Caspi,2 Fabrice P. Cordelières,1 Jim P. Dompierre,1 Denis L. Dujardin,1,{dagger} Cynthia Koifman,2 Patrick Martin,1 Casper C. Hoogenraad,3 Anna Akhmanova,3 Niels Galjart,3 Jan R. De Mey,1 and Orly Reiner2*

Institut Curie, Section de Recherche, CNRS-UMR 146, Centre Universitaire d'Orsay, 91405 Orsay Cedex, France,1 Department of Molecular Genetics, The Weizmann Institute of Science, 76100 Rehovot, Israel,2 Department of Cell Biology and Genetics, Erasmus University, 3000 DR Rotterdam, The Netherlands3

Received 10 October 2001/ Returned for modification 7 December 2001/ Accepted 15 January 2002

CLIP-170 is a plus-end tracking protein which may act as an anticatastrophe factor. It has been proposed to mediate the association of dynein/dynactin to microtubule (MT) plus ends, and it also binds to kinetochores in a dynein/dynactin-dependent fashion, both via its C-terminal domain. This domain contains two zinc finger motifs (proximal and distal), which are hypothesized to mediate protein-protein interactions. LIS1, a protein implicated in brain development, acts in several processes mediated by the dynein/dynactin pathway by interacting with dynein and other proteins. Here we demonstrate colocalization and direct interaction between CLIP-170 and LIS1. In mammalian cells, LIS1 recruitment to kinetochores is dynein/dynactin dependent, and recruitment there of CLIP-170 is dependent on its site of binding to LIS1, located in the distal zinc finger motif. Overexpression of CLIP-170 results in a zinc finger-dependent localization of a phospho-LIS1 isoform and dynactin to MT bundles, raising the possibility that CLIP-170 and LIS1 regulate dynein/dynactin binding to MTs. This work suggests that LIS1 is a regulated adapter between CLIP-170 and cytoplasmic dynein at sites involved in cargo-MT loading, and/or in the control of MT dynamics.

* Corresponding author. Mailing address: Department of Molecular Genetics, The Weizmann Institute of Science, 76100 Rehovot, Israel. Phone: 972 8 9342319. Fax: 972 8 9344108. E-mail: orly.reiner{at}weizmann.ac.il.

{dagger} Present address: Department of Pathology, Columbia University, New York, NY 10032-3702.

Molecular and Cellular Biology, May 2002, p. 3089-3102, Vol. 22, No. 9
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.9.3089-3102.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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