CHL1 promotes Sema3A-induced growth cone collapse and neurite elaboration through a motif required for recruitment of ERM proteins to the plasma membrane

J Neurochem. 2008 Feb;104(3):731-44. doi: 10.1111/j.1471-4159.2007.05013.x. Epub 2007 Nov 6.

Abstract

Close homolog of L1 (CHL1) is a transmembrane cell adhesion molecule with unique developmental functions in cortical neuronal positioning and dendritic projection within the L1 family, as well as shared functions in promotion of integrin-dependent neurite outgrowth and semaphorin3A (Sema3A)-mediated axon repulsion. The molecular mechanisms by which CHL1 mediates these diverse functions are obscure. Here it is demonstrated using a cytofluorescence assay that CHL1 is able to recruit ezrin, a member of the ezrin-radixin-moesin (ERM) family of filamentous actin binding proteins to the plasma membrane, and that this requires a membrane-proximal motif (RGGKYSV) in the CHL1 cytoplasmic domain. This sequence in CHL1 is shown to have novel functions necessary for Sema3A-induced growth cone collapse and CHL1-dependent neurite outgrowth and branching in cortical embryonic neurons. In addition, stimulation of haptotactic cell migration and cellular adhesion to fibronectin by CHL1 depends on the CHL1/ERM recruitment motif. These findings suggest that a direct or indirect interaction between CHL1 and ERM proteins mediates Sema3A-induced growth cone collapse as well as neurite outgrowth and branching, which are essential determinants of axon guidance and connectivity in cortical development.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion / drug effects
  • Cell Adhesion / physiology
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / physiology*
  • Cell Membrane / metabolism*
  • Cell Movement / drug effects
  • Cell Movement / physiology
  • Cells, Cultured
  • Cerebral Cortex
  • Cytoskeletal Proteins / metabolism
  • DNA-Binding Proteins / metabolism*
  • Embryo, Mammalian
  • Fibronectins / physiology
  • Green Fluorescent Proteins / metabolism
  • Growth Cones / drug effects*
  • Growth Cones / physiology
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neurites / chemistry
  • Neurites / physiology*
  • Neurons / cytology*
  • Neurons / metabolism*
  • Rats
  • Semaphorin-3A / pharmacology*
  • Transcription Factors / metabolism*
  • Transfection / methods

Substances

  • Cell Adhesion Molecules
  • Chl1 protein, mouse
  • Cytoskeletal Proteins
  • DNA-Binding Proteins
  • Etv5 protein, mouse
  • Fibronectins
  • Semaphorin-3A
  • Transcription Factors
  • ezrin
  • Green Fluorescent Proteins