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Broad specificity of GDNF family receptors GFRα1 and GFRα2 for GDNF and NTN in neurons and transfected cells
Author(s) -
Wang LiChong,
Shih Ai,
Hongo Joanne,
Devaux Brigitte,
Hynes Mary
Publication year - 2000
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/1097-4547(20000701)61:1<1::aid-jnr1>3.0.co;2-j
Subject(s) - glial cell line derived neurotrophic factor , gdnf family of ligands , neurturin , neurotrophic factors , proto oncogene proteins c ret , microbiology and biotechnology , dopaminergic , receptor , biology , chemistry , neuroscience , biochemistry , dopamine
The glial cell line‐derived neurotrophic factor (GDNF) family of ligands binds to lipid anchored proteins termed GDNF family receptor (GFR)αs, and then activates the RET receptor tyrosine kinase, by ligand GFRα. The binding of soluble GFRαs to transfected cells suggested that different GFRαs were dedicated to particular ligands, with GDNF acting primarily or entirely through GFRα1, and neurturin (NTN), through GFRα2. More recent evidence has suggested the possibility of cross‐talk between these ligands and the two receptors. We examined here whether crosstalk between the GDNF ligands and the GFRαs is biologically relevant, using midbrain dopaminergic, and parasympathetic, submandibular gland neurons. By biochemical and genetic addition and/or deletion of GFRα1 and 2, we show that in both neuronal cell types, robust biological activities of GDNF or NTN can be mediated by either GFRα1 or GFRα2, although GDNF is slightly more potent in dopaminergic (DA) neurons which normally express GFRα1, and NTN in submandibular neurons which normally express GFRα2. Throughout the body, GDNF and NTN are likely to have important biological actions on both GFRα1‐ and GFRα2‐expressing cells. J. Neurosci. Res. 61:1–9, 2000. © 2000 Wiley‐Liss, Inc.