LIS1, CLIP-170's key to the dynein/dynactin pathway.
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.
Coquelle
Frédéric M
FM
Institut Curie, Section de Recherche, CNRS-UMR 146, Centre Universitaire d'Orsay, 91405 Orsay Cedex, France.
Caspi
Michal
M
Cordelières
Fabrice P
FP
Dompierre
Jim P
JP
Dujardin
Denis L
DL
Koifman
Cynthia
C
Martin
Patrick
P
Hoogenraad
Casper C
CC
Akhmanova
Anna
A
Galjart
Niels
N
De Mey
Jan R
JR
Reiner
Orly
O
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000818:Animals; D019556:COS Cells; D000072159:Dynactin Complex; D004398:Dyneins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007399:Interphase; D018386:Kinetochores / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D009363:Neoplasm Proteins; D011485:Protein Binding; D020033:Protein Isoforms / Q000378:metabolism; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D016335:Zinc Fingers
D000072159:Dynactin Complex; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D020033:Protein Isoforms; C076744:cytoplasmic linker protein 170; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C084102:PAFAH1B1 protein, human; D004398:Dyneins