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

Mol Cell Biol. 2002 May;22(9):3089-102. doi: 10.1128/MCB.22.9.3089-3102.2002.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Alkyl-2-acetylglycerophosphocholine Esterase
  • Animals
  • COS Cells
  • Dynactin Complex
  • Dyneins / metabolism*
  • HeLa Cells
  • Humans
  • Interphase
  • Kinetochores / metabolism
  • Microscopy, Fluorescence
  • Microtubule-Associated Proteins / metabolism*
  • Microtubules / metabolism
  • Neoplasm Proteins
  • Protein Binding
  • Protein Isoforms / metabolism
  • Protein Structure, Tertiary
  • Signal Transduction
  • Zinc Fingers

Substances

  • Dynactin Complex
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • Protein Isoforms
  • cytoplasmic linker protein 170
  • 1-Alkyl-2-acetylglycerophosphocholine Esterase
  • PAFAH1B1 protein, human
  • Dyneins