TY - JOUR
T1 - TrnR2, a novel receptor that mediates neurturin and GDNF signaling through Ret
AU - Baloh, Robert H.
AU - Tansey, Malú G.
AU - Golden, Judith P.
AU - Creedon, Douglas J.
AU - Heuckeroth, Robert O.
AU - Keck, Catherine L.
AU - Zimonjic, Drazen B.
AU - Popescu, Nicholas C.
AU - Johnson, Eugene M.
AU - Milbrandt, Jeffrey
N1 - Funding Information:
We thank P. Osborne, P. Lampe, T. Fahrner, K. Simburger, and S. Audraine for their outstanding technical support. We also thank D. Wright and A. Parsidanian for the Ret and TrnR1 in situ probes, and T. Araki for advice and support in nerve injury studies. This work was supported by National Institutes of Health Grants R01 AG13729 and R01 AG13730, and Genentech. Washington University, E. M. J., and J. M. may receive income based on a license to Genentech. J. M. is an Established Investigator of the American Heart Association.
PY - 1997/5
Y1 - 1997/5
N2 - Glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) comprise a family of TGF-β-related neurotrophic factors (TRNs), which have trophic influences on a variety of neuronal populations. A receptor complex comprised of TrnR1 (GDNFRα) 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 ~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.
AB - Glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) comprise a family of TGF-β-related neurotrophic factors (TRNs), which have trophic influences on a variety of neuronal populations. A receptor complex comprised of TrnR1 (GDNFRα) 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 ~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.
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U2 - 10.1016/S0896-6273(00)80318-9
DO - 10.1016/S0896-6273(00)80318-9
M3 - Article
C2 - 9182803
AN - SCOPUS:0030983548
SN - 0896-6273
VL - 18
SP - 793
EP - 802
JO - Neuron
JF - Neuron
IS - 5
ER -