Cloning, mRNA distribution and chromosomal localisation of the gene for glial cell line-derived neurotrophic factor receptor beta, a homologue to GDNFR-alpha.
Glial cell line-derived neurotrophic factor (GDNF) is a potent survival factor for central dopaminergic neurons, motor neurons and several other populations of neurons in the central and peripheral nervous system. GDNF and its receptor complex of c-RET tyrosine kinase and a glycosyl-phosphatidylinositol linked protein GDNFR-alpha are of great interest due to their potential use in the therapy of Parkinson's and motoneuron diseases. We have cloned the human and rat cDNA sequences of GDNFR-beta, a new gene encoding for a 464 amino acid long homologue of GDNFR-alpha, and assign the locus of this new gene to human chromosome 8p21-22 and mouse chromosome 14D3-E1. Similarly to GDNFR-alpha, GDNFR-beta mediates GDNF-induced Ret autophosphorylation in transfected cells. By northern hybridisation we show that the transcript level of human GDNFR-beta mRNA is high in the adult brain, intestine and placenta and in fetal brain, lung and kidney. Studied by in situ hybridisation, GDNFR-beta mRNA shows in E17 rat embryo different distribution to that of GDNFR-alpha mRNA, especially, in adrenal gland, kidney and gut. In the developing nervous system, GDNFR-beta mRNA expression is restricted to certain neuronal populations, while GDNFR-alpha mRNA is widely expressed also in non-neuronal cells. The distinct tissue distribution of GDNFR-beta mRNA and its ability to mediate GDNF signal in transfected cells suggest a role in signal transduction of GDNF and, possibly, related neurotrophic factors in vivo.
Suvanto
P
P
Institute of Biotechnology, University of Helsinki, Finland. petro.suvanto@helsinki.fi
Wartiovaara
K
K
Lindahl
M
M
Arumae
U
U
Moshnyakov
M
M
Horelli-Kuitunen
N
N
Airaksinen
M S
MS
Palotie
A
A
Sariola
H
H
Saarma
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002460:Cell Line; D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8; D003001:Cloning, Molecular; D004247:DNA; D029721:Drosophila Proteins; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000494:pharmacology; D009457:Neuroglia / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D012333:RNA, Messenger; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics*
D029721:Drosophila Proteins; C495039:GDNF protein, human; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D004247:DNA; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila; C495001:Ret protein, rat