RGM and its receptor neogenin regulate neuronal survival

Nat Cell Biol. 2004 Aug;6(8):749-55. doi: 10.1038/ncb1157. Epub 2004 Jul 18.

Abstract

Repulsive guidance molecule (RGM) is an axon guidance protein that repels retinal axons upon activation of the neogenin receptor. To understand the functions of RGM-neogenin complexes in vivo, we used gene transfer technology to perturb their expression in the developing neural tube of chick embryos. Surprisingly, neogenin over-expression or RGM down-expression in the neural tube induces apoptosis. Neogenin pro-apoptotic activity in immortalized neuronal cells and in the neural tube is associated with the cleavage of its cytoplasmic domain by caspases. Thus neogenin is a dependence receptor inducing cell death in the absence of RGM, whereas the presence of RGM inhibits this effect.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis
  • Avian Proteins / genetics
  • Avian Proteins / metabolism*
  • Caspases / metabolism
  • Cell Survival
  • Cells, Cultured
  • Chick Embryo*
  • Chickens
  • Down-Regulation
  • Enzyme Activation
  • Gene Expression Regulation, Developmental*
  • Green Fluorescent Proteins
  • Immunohistochemistry
  • In Situ Hybridization
  • Luminescent Proteins / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mutagenesis, Site-Directed
  • Neurons / cytology
  • Neurons / physiology*
  • RNA, Small Interfering / metabolism
  • Rats

Substances

  • Avian Proteins
  • Luminescent Proteins
  • Membrane Proteins
  • RNA, Small Interfering
  • neogenin
  • Green Fluorescent Proteins
  • Caspases