GDNF and GFRalpha: a versatile molecular complex for developing neurons

Trends Neurosci. 2008 Aug;31(8):384-91. doi: 10.1016/j.tins.2008.05.003. Epub 2008 Jul 1.


The GDNF family ligands (GFLs) signal through the canonical signaling receptor Ret and a glycosyl-phosphatidylinositol-anchored co-receptor, GFRalpha. In recent years, signaling by GFLs has been shown to be more complex than originally assumed. The discrepant expression between GFRalphas and Ret has suggested the existence of additional signal-transducing GDNF receptors, such as NCAM. Here we summarize novel functions and Ret-independent signaling mechanisms for GDNF and GFRalpha, focusing on developing neurons. Emerging evidence indicates a prominent role of GDNF and GFRalpha in the control of neuroblast migration and chemoattraction and in the formation of neuronal synapses by a new mechanism of ligand-induced cell adhesion. Therefore, these data highlight the importance of this versatile molecular complex for nervous system development, function and regeneration.

Publication types

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

MeSH terms

  • Animals
  • Cell Adhesion
  • Cell Differentiation / physiology
  • Glial Cell Line-Derived Neurotrophic Factor Receptors / metabolism*
  • Glial Cell Line-Derived Neurotrophic Factors / metabolism*
  • Humans
  • Nervous System / growth & development
  • Nervous System / metabolism
  • Neurons / cytology
  • Neurons / metabolism*
  • Proto-Oncogene Proteins c-ret / metabolism*
  • Second Messenger Systems / physiology
  • Signal Transduction / physiology*


  • Glial Cell Line-Derived Neurotrophic Factor Receptors
  • Glial Cell Line-Derived Neurotrophic Factors
  • Proto-Oncogene Proteins c-ret