LINGO-1 regulates oligodendrocyte differentiation by inhibiting ErbB2 translocation and activation in lipid rafts

Mol Cell Neurosci. 2014 May;60:36-42. doi: 10.1016/j.mcn.2014.02.006. Epub 2014 Feb 28.

Abstract

Oligodendrocyte differentiation is negatively regulated by LINGO-1 and positively regulated by the ErbB2 receptor tyrosine kinase. In wild-type oligodendrocytes, inhibition of ErbB2 blocks differentiation, whereas activation of ErbB2 promotes differentiation. In LINGO-1(-/-) oligodendrocytes, inhibition of ErbB2 blocks oligodendrocyte differentiation; whereas activation of ErbB2 does not enhance differentiation. Biological and biochemical evidence showing that LINGO-1 can directly bind to ErbB2, block ErbB2 translocation into lipid rafts, and inhibit its phosphorylation for activation. The study demonstrates a novel regulatory mechanism of ErbB2 function whereby LINGO-1 suppresses oligodendrocyte differentiation by inhibiting ErbB2 translocation and activation in lipid rafts.

Keywords: ErbB2; LINGO-1; Lipid raft; Multiple sclerosis; Oligodendrocyte.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells
  • Cells, Cultured
  • Cricetinae
  • Cricetulus
  • Humans
  • Membrane Microdomains / metabolism*
  • Membrane Proteins / metabolism*
  • Mice
  • Nerve Tissue Proteins / metabolism*
  • Neurogenesis*
  • Oligodendroglia / cytology
  • Oligodendroglia / metabolism*
  • Phosphorylation
  • Protein Binding
  • Protein Transport
  • Receptor, ErbB-2 / metabolism*

Substances

  • LINGO1 protein, human
  • Membrane Proteins
  • Nerve Tissue Proteins
  • ERBB2 protein, human
  • Receptor, ErbB-2