IndraLab

"The GDNF:GFRα1 complex is also able to bind to NCAM with high affinity to activate SFKs and FAK xref ."

"In this last section, we turn our attention to some of the possible implications of the interactions between GDNF, GFRα1, and NCAM for development in vivo."

"NCAM binds GFRα1 and GDNF and downregulates NCAM-mediated cell adhesion, which activates cytoplasmic protein tyrosine kinase signaling in the absence of RET."

"GFRa1 and GDNF interact with NCAM in neurons and Schwann cells to promote neurite outgrowth and Schwann cell migration ( xref ; xref )."

"Both proteins are coexpressed in the developing nephron, midbrain and motor neurons and mice carrying a disruption of either Ret or GFRα1 are deficient in renal and neuronal development and suffer from early postnatal death. xref GDNF/Ret signalling through the phosphatidylinositol 3-kinase/nuclear factor kappa B pathway is required for mitochondrial function and morphology, xref and seems also relevant for dopamine system maintenance to prevent Parkinson’s and Hirschsprung diseases. xref Besides, it has been reported that p140 NCAM may interact with GFRα1 to mediate GDNF signalling independently from Ret in Schwann cell migration. xref Another study also describes that GDNF can regulate migration of GABAergic cells in the medial ganglionic eminence and cortex via GFRα1, but not Ret or NCAM. xref Finally, an inverse relationship between GFRα1 and Ret has been reported in dopaminergic neurons, where knocking down Ret leads to increased GFRα1 expression. xref "

"In addition to promoting high-affinity binding of GDNF ligands, the association of GFRα1 with NCAM prevented homophilic NCAM-NCAM interactions (Paratcha et al. xref ), illustrating the ability of GFRα1 to transform NCAM from a short-range cell adhesion molecule into a long-range signaling receptor for diffusible GDNF ligands."