In the brain, predominantly expressed in the striatum with highest levels in the caudate and lowest in the putamen. Isoform 2 is absent from most tissues except for low levels in intestine and kidney. Highest expression of isoform 3 is found in pancreatic islets. Isoform 5 is expressed at very low levels in putamen, nucleus accumbens, prefrontal cortex, amygdala, hypothalamus and intestine. Isoform 3 is up-regulated in the middle temporal gyrus of Alzheimer disease patients while isoform 2 shows no change.
Function
Neurotrophic factor that enhances survival and morphological differentiation of dopaminergic neurons and increases their high-affinity dopamine uptake. Acts by binding to its coreceptor, GFRA1, leading to autophosphorylation and activation of the RET receptor. Involved in the development of the neural crest.
