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glial-derived neurotrophic factor; hGDNF; astrocyte-derived trophic factor; ATF (GDNF)

Function: - neurotrophic for midbrain dopaminergic neurons - increases high-affinity dopamine uptake of dopaminergic neurons - mediates activation of c-ret protein [2,3] Structure: - secreted as disulfide-linked homodimer - belongs to the TGF-beta family, GDNF subfamily Compartment: secreted Expression: - in the brain, predominantly expressed in the striatum - highest expression in the caudate - lowest expresion in the putamen - isoform 2 is absent from most tissues except for low levels in intestine & 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 & intestine - induced by cAMP, 12-O-tetradecanoylphorbol-13-acetate (TPA) & FGF2 Pathology: - mice defective in GDNF expression show renal agenesis & absence of enteric nervous system [4,5,6] - isoform 3 is up-regulated in the middle temporal gyrus of patients with Alzheimer's disease - isoform 2 shows no change - defects in GDNF may be a cause of Hirschsprung disease type 3 - defects in GDNF are a cause of congenital central hypoventilation syndrome

Interactions

molecular events

Related

glial derived neurotrophic factor [GDNF] receptor glial derived neurotrophic factor [GDNF] receptor alpha proto-oncogene tyrosine-protein kinase receptor ret; C-ret; (RET, CDHF12)

General

growth factor oligomerizing protein secreted protein TGF-beta family protein

Properties

SIZE: entity length = 211 aa MW = 24 kD COMPARTMENT: extracellular compartment MOTIF: signal sequence {1-19} cysteine residue {C118} MODIFICATION: cysteine residue {C179} N-glycosylation site {N126} cysteine residue {C145} MODIFICATION: cysteine residue {C208} cysteine residue {C149} MODIFICATION: cysteine residue {C210} N-glycosylation site {N162} cysteine residue {C178} MODIFICATION: cysteine residue {C-INTERCHAIN} cysteine residue {C179} MODIFICATION: cysteine residue {C118} cysteine residue {C208} MODIFICATION: cysteine residue {C145} cysteine residue {C210} MODIFICATION: cysteine residue {C149} SECRETED-BY: neuroglia

Database Correlations

OMIM correlations MORBIDMAP 600837 UniProt P39905 Pfam PF00019 Entrez Gene 2668 Kegg hsa:2668

References

  1. Lin LF, Doherty DH, Lile JD, Bektesh S, Collins F. GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons. Science. 1993 May 21;260(5111):1130-2. PMID: 8493557
  2. Trupp M et al Functional receptor for GDNF encoded by the c-ret proto- oncogene. Nature. 1996 Jun 27;381(6585):785-9. PMID: 8657281
  3. Durbec P, Marcos-Gutierrez CV, Kilkenny C, Grigoriou M, Wartiowaara K, Suvanto P, Smith D, Ponder B, Costantini F, Saarma M, et al. GDNF signalling through the Ret receptor tyrosine kinase. Nature. 1996 Jun 27;381(6585):789-93. PMID: 8657282
  4. Sanchez MP, Silos-Santiago I et al Renal agenesis and the absence of enteric neurons in mice lacking GDNF. Nature. 1996 Jul 4;382(6586):70-3. PMID: 8657306
  5. Pichel JG, Shen L, Sheng HZ, Granholm AC, Drago J, Grinberg A, Lee EJ, Huang SP, Saarma M, Hoffer BJ, Sariola H, Westphal H. Defects in enteric innervation and kidney development in mice lacking GDNF. Nature. 1996 Jul 4;382(6586):73-6. PMID: 8657307
  6. Moore MW et al Reichardt LF, Ryan AM, Carver-Moore K, Rosenthal A. Renal and neuronal abnormalities in mice lacking GDNF. Nature. 1996 Jul 4;382(6586):76-9. PMID: 8657308
  7. UniProt :accession P39905
  8. R&D systems' cytokine mini-reviews: GDNF http://www.rndsystems.com/molecule_detail.aspx?m=1510
  9. GeneReviews http://www.ncbi.nlm.nih.gov/sites/genetests/lab/gene/GDNF