ADF/cofilin controls cell polarity during fibroblast migration

Curr Biol. 2003 Feb 4;13(3):252-7. doi: 10.1016/s0960-9822(03)00040-x.

Abstract

To migrate, normally a cell must establish morphological polarity and continuously protrude a single lamellipodium, polarized in the direction of migration. We have previously shown that actin filament disassembly is necessary for protrusion of the lamellipodium during fibroblast migration. As ADF/cofilin (AC) proteins are essential for the catalysis of filament disassembly in cells, we assessed their role in polarized lamellipodium protrusion in migrating fibroblasts. We compared the spatial distribution of AC and the inactive, phosphorylated AC (pAC) in migrating cells. AC, but not pAC, localized to the lamellipodium. To investigate a role for AC in cell polarity, we increased the proportion of pAC in migrating fibroblasts by overexpressing constitutively active (CA) LIM kinase 1. In 87% of cells expressing CA LIM kinase, cell polarity was abolished. In such cells, the single polarized lamellipodium was replaced by multiple nonpolarized lamellipodia, which, in contrast to nonexpressing migrating cells, stained for pAC. Cell polarity was rescued by coexpressing an active, nonphosphorylatable Xenopus AC (CA XAC) with the CA LIMK. Furthermore, overexpressing a pseudophosphorylated (less active) XAC by itself also abolished cell polarity. We conclude that locally maintaining ADF/cofilin in the active, nonphosphorylated state within the lamellipodium is necessary to maintain polarized protrusion during cell migration.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actin Depolymerizing Factors
  • Actins / metabolism
  • Animals
  • Cell Movement / physiology*
  • Cell Polarity*
  • Chick Embryo
  • Destrin
  • Fibroblasts / cytology
  • Fibroblasts / metabolism*
  • Lim Kinases
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism*
  • Phosphorylation
  • Protein Kinases / genetics
  • Protein Kinases / metabolism
  • Pseudopodia / metabolism
  • Xenopus Proteins / genetics
  • Xenopus Proteins / metabolism
  • Xenopus laevis

Substances

  • Actin Depolymerizing Factors
  • Actins
  • Destrin
  • Microfilament Proteins
  • Xenopus Proteins
  • Protein Kinases
  • Lim Kinases