F-spondin regulates neuronal survival through activation of disabled-1 in the chicken ciliary ganglion

Mol Cell Neurosci. 2011 Feb;46(2):483-97. doi: 10.1016/j.mcn.2010.12.001. Epub 2010 Dec 9.

Abstract

The extracellular membrane-associated protein F-spondin has been implicated in cell-matrix and cell-cell adhesion and plays an important role in axonal pathfinding. We report here that F-spondin is expressed in non-neuronal cells in the embryonic chicken ciliary ganglion (CG) and robustly promotes survival of cultured CG neurons. Using deletion constructs of F-spondin we found that the amino-terminal Reelin/Spondin domain cooperates with thrombospondin type 1 repeat (TSR) 6, a functional TGFβ-activation domain. In ovo treatment with blocking antibodies raised against the Reelin/Spondin domain or the TSR-domains caused increased apoptosis of CG neurons during the phase of programmed cell death and loss of about 30% of the neurons compared to controls. The Reelin/Spondin domain receptor - APP and its downstream signalling molecule disabled-1 are expressed in CG neurons. F-spondin induced rapid phosphorylation of disabled-1. Moreover, both blocking the central APP domain and interference with disabled-1 signalling disrupted the survival promoting effect of F-spondin. Taken together, our data suggest that F-spondin can promote neuron survival by a mechanism involving the Reelin/Spondin and the TSR domains.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Apoptosis / physiology
  • Cell Survival
  • Chick Embryo
  • Extracellular Matrix Proteins / metabolism*
  • Ganglia, Parasympathetic / embryology
  • Ganglia, Parasympathetic / metabolism*
  • Humans
  • Immunoblotting
  • Immunohistochemistry
  • In Situ Hybridization
  • In Situ Nick-End Labeling
  • Nerve Tissue Proteins / metabolism*
  • Neurogenesis / physiology*
  • Neurons / cytology
  • Neurons / metabolism*
  • Transfection

Substances

  • Adaptor Proteins, Signal Transducing
  • Extracellular Matrix Proteins
  • Nerve Tissue Proteins