LIS1, CLIP-170's key to the dynein/dynactin pathway |
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Authors: | Coquelle Frédéric M Caspi Michal Cordelières Fabrice P Dompierre Jim P Dujardin Denis L Koifman Cynthia Martin Patrick Hoogenraad Casper C Akhmanova Anna Galjart Niels De Mey Jan R Reiner Orly |
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Affiliation: | Institut Curie, Section de Recherche, CNRS-UMR 146, Centre Universitaire d'Orsay, 91405 Orsay Cedex, France. |
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Abstract: | 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. |
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