TrnR2, a novel receptor that mediates neurturin and GDNF signaling through Ret.
Glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) comprise a family of TGF-beta-related neurotrophic factors (TRNs), which have trophic influences on a variety of neuronal populations. A receptor complex comprised of TrnR1 (GDNFR alpha) and Ret was recently identified and found to be capable of mediating both GDNF and NTN signaling. We have identified a novel receptor based on homology to TrnR1, called TrnR2, that is 48% identical to TrnR1, and is located on the short arm of chromosome 8. TrnR2 is attached to the cell surface via a GPI-linkage, and can mediate both NTN and GDNF signaling through Ret in vitro. Fibroblasts expressing TrnR2 and Ret are approximately 30-fold more sensitive to NTN than to GDNF treatment, whereas those expressing TrnR1 and Ret respond equivalently to both factors, suggesting the TrnR2-Ret complex acts preferentially as a receptor for NTN. TrnR2 and Ret are expressed in neurons of the superior cervical and dorsal root ganglia, and in the adult brain. Comparative analysis of TrnR1, TrnR2, and Ret expression indicates that multiple receptor complexes, capable of mediating GDNF and NTN signaling, exist in vivo.
Baloh
R H
RH
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Tansey
M G
MG
Golden
J P
JP
Creedon
D J
DJ
Heuckeroth
R O
RO
Keck
C L
CL
Zimonjic
D B
DB
Popescu
N C
NC
Johnson
E M
EM
Milbrandt
J
J
D016475:3T3 Cells / Q000737:chemistry / Q000378:metabolism; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D015152:Blotting, Northern; D001923:Brain Chemistry / Q000502:physiology; D002874:Chromosome Mapping; D029721:Drosophila Proteins; D015870:Gene Expression / Q000502:physiology; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology*; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D051101:Neurturin; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051096:Proto-Oncogene Proteins c-ret; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology*; D012584:Sciatic Nerve / Q000737:chemistry / Q000166:cytology / Q000293:injuries; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D013737:Testis / Q000737:chemistry; D015854:Up-Regulation / Q000502:physiology
D029721:Drosophila Proteins; C495040:Gdnf protein, mouse; 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; D051101:Neurturin; C495056:Nrtn protein, mouse; C495057:Nrtn protein, rat; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila; C494999:Ret protein, mouse; C495001:Ret protein, rat