GDNF Active Protein

This gene encodes a highly conserved neurotrophic factor. The recombinant form of this protein was shown to promote the survival and differentiation of dopaminergic neurons in culture, and was able to prevent apoptosis of motor neurons induced by axotomy. The encoded protein is processed to a mature secreted form that exists as a homodimer. The mature form of the protein is a ligand for the product of the RET (rearranged during transfection) protooncogene. Multiple transcript variants encoding different isoforms have been found for this gene. Mutations in this gene may be associated with Hirschsprung disease. [provided by RefSeq, Jun 2010]

GDNF: Neurotrophic factor that enhances survival and morphological differentiation of dopaminergic neurons and increases their high-affinity dopamine uptake. Defects in GDNF may be a cause of Hirschsprung disease type 3 (HSCR3). In association with mutations of RET gene, defects in GDNF may be involved in Hirschsprung disease. This genetic disorder of neural crest development is characterized by the absence of intramural ganglion cells in the hindgut, often resulting in intestinal obstruction. Defects in GDNF are a cause of congenital central hypoventilation syndrome (CCHS); also known as congenital failure of autonomic control or Ondine curse. CCHS is a rare disorder characterized by abnormal control of respiration in the absence of neuromuscular or lung disease, or an identifiable brain stem lesion. A deficiency in autonomic control of respiration results in inadequate or negligible ventilatory and arousal responses to hypercapnia and hypoxemia. Belongs to the TGF-beta family. GDNF subfamily. 5 isoforms of the human protein are produced by alternative splicing.

Protein type: Secreted; Secreted, signal peptide

Chromosomal Location of Human Ortholog: 5p13.1-p12

Cellular Component: extracellular region

Molecular Function: protein homodimerization activity; growth factor activity; receptor binding

Biological Process: nervous system development; axon guidance; positive regulation of dopamine secretion; peristalsis; adult locomotory behavior; mRNA stabilization; regulation of dopamine uptake; positive regulation of monooxygenase activity; signal transduction; enteric nervous system development; sympathetic nervous system development; regulation of gene expression; ureteric bud branching; induction of an organ; positive regulation of cell proliferation; postganglionic parasympathetic nervous system development; positive regulation of transcription from RNA polymerase II promoter; negative regulation of neuron apoptosis; positive regulation of cell differentiation; postsynaptic membrane organization; metanephros development; neural crest cell migration; neurite development; negative regulation of apoptosis

Disease: Hirschsprung Disease, Susceptibility To, 3; Central Hypoventilation Syndrome, Congenital; Pheochromocytoma