Glial Cell Line Derived Neurotrophic Factor Receptor Alpha 1 (GFRa1)

GFRA1 is released by neuronal cells, Schwann cells, and injured sciatic nerve. RET stimulation in trans by soluble or immobilized GFRA1 potentiates downstream signaling, neurite outgrowth, and neuronal survival, and elicits dramatic localized expansions of axons and growth cones.

Soluble GFRA1 mediates robust recruitment of RET to lipid rafts via a mechanism requiring the RET tyrosine kinase. Activated RET associates with different adaptor proteins inside and outside lipid rafts. The authors concluded that these results provide an explanation of the tissue distribution of GFRA1, supporting the physiologic importance of RET activation in trans as a mechanism to potentiate and diversify the biologic responses to GDNF.