GDNF and GFRalpha: a versatile molecular complex for developing neurons.
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.
Paratcha
Gustavo
G
Laboratory of Molecular and Cellular Neuroscience, Department of Neuroscience, Karolinska Institute, S-17177 Stockholm, Sweden. gustavo.paratcha@ki.se
Ledda
Fernanda
F
D000818:Animals; D002448:Cell Adhesion; D002454:Cell Differentiation / Q000502:physiology; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors / Q000378:metabolism*; D051098:Glial Cell Line-Derived Neurotrophic Factors / Q000378:metabolism*; D006801:Humans; D009420:Nervous System / Q000254:growth & development / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D051096:Proto-Oncogene Proteins c-ret / Q000378:metabolism*; D015290:Second Messenger Systems / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*
D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D051098:Glial Cell Line-Derived Neurotrophic Factors; D051096:Proto-Oncogene Proteins c-ret