Par-3 mediates the inhibition of LIM kinase 2 to regulate cofilin phosphorylation and tight junction assembly

J Cell Biol. 2006 Feb 27;172(5):671-8. doi: 10.1083/jcb.200510061.

Abstract

The polarity protein Par-3 plays critical roles in axon specification and the establishment of epithelial apico-basal polarity. Par-3 associates with Par-6 and atypical protein kinase C and is required for the proper assembly of tight junctions, but the molecular basis for its functions is poorly understood. We now report that depletion of Par-3 elevates the phosphorylated pool of cofilin, a key regulator of actin dynamics. Expression of a nonphosphorylatable mutant of cofilin partially rescues tight junction assembly in cells lacking Par-3, as does the depletion of LIM kinase 2 (LIMK2), an upstream kinase for cofilin. Par-3 binds to LIMK2 but not to the related kinase LIMK1. Par-3 inhibits LIMK2 activity in vitro, and overexpressed Par-3 suppresses cofilin phosphorylation that is induced by lysophosphatidic acid. Our findings identify LIMK2 as a novel target of Par-3 and uncover a molecular mechanism by which Par-3 could regulate actin dynamics during cell polarization.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Actin Depolymerizing Factors / genetics
  • Actin Depolymerizing Factors / metabolism*
  • Animals
  • COS Cells
  • Caenorhabditis elegans Proteins / physiology*
  • Cell Line
  • Cell Line, Tumor
  • Cell Polarity / genetics
  • Cell Polarity / physiology*
  • Chlorocebus aethiops
  • DNA-Binding Proteins / antagonists & inhibitors*
  • DNA-Binding Proteins / physiology
  • Dogs
  • Enzyme Inhibitors* / pharmacology
  • HeLa Cells
  • Humans
  • Lim Kinases
  • Mutagenesis, Site-Directed
  • Phosphorylation
  • Protein Serine-Threonine Kinases
  • Tight Junctions / metabolism*
  • Tight Junctions / physiology

Substances

  • Actin Depolymerizing Factors
  • Caenorhabditis elegans Proteins
  • DNA-Binding Proteins
  • Enzyme Inhibitors
  • LIMK2 protein, human
  • Lim Kinases
  • PAR-3 protein, C elegans
  • Protein Serine-Threonine Kinases