A novel p75 neurotrophin receptor-related protein, NRH2, regulates nerve growth factor binding to the TrkA receptor.
Nerve growth factor (NGF) functions as a ligand for two receptors, the TrkA tyrosine kinase receptor and the p75 neurotrophin receptor (p75NTR). The Ig-like domains of Trk receptors and the cysteine-rich repeats of p75NTR are involved in binding to the neurotrophins. Recently, a closely related gene to p75NTR called neurotrophin receptor homolog-2 (NRH2) was identified; however, the function of NRH2 and its relevance to neurotrophin signaling are unclear. NRH2 contains a similar transmembrane and intracellular domain as p75NTR but lacks the characteristic cysteine-rich repeats in the extracellular domain. Here we show that NRH2 is expressed in several neuronal populations that also express p75NTR and Trk receptors. NRH2 does not bind to NGF; however, coimmunoprecipitation experiments demonstrate that NRH2 is capable of interacting with TrkA receptors. Coexpression of NRH2 with TrkA receptors resulted in the formation of high-affinity binding sites for NGF. These results indicate that a transmembrane protein related to p75NTR is capable of modulating Trk receptor binding properties.
Murray
Simon S
SS
Skirball Institute of Bimolecular Medicine, New York University School of Medicine, New York, New York 10016, USA. s.murray@hfi.unimelb.edu.au
Perez
Pilar
P
Lee
Ramee
R
Hempstead
Barbara L
BL
Chao
Moses V
MV
D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D003432:Cross-Linking Reagents / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D020932:Nerve Growth Factor / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D009928:Organ Specificity; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D051381:Rats; D020800:Receptor, Nerve Growth Factor; D020917:Receptor, trkA / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000235:genetics* / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013116:Spinal Cord / Q000378:metabolism
D003432:Cross-Linking Reagents; C476128:NRH2 protein, mouse; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D020932:Nerve Growth Factor; D020917:Receptor, trkA