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Publication : LIS1, CLIP-170's key to the dynein/dynactin pathway.

First Author  Coquelle FM Year  2002
Journal  Mol Cell Biol Volume  22
Issue  9 Pages  3089-102
PubMed ID  11940666 Mgi Jnum  J:128546
Mgi Id  MGI:3767478 Doi  10.1128/MCB.22.9.3089-3102.2002
Citation  Coquelle FM, et al. (2002) LIS1, CLIP-170's key to the dynein/dynactin pathway. Mol Cell Biol 22(9):3089-102
abstractText  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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