The neuropeptide head activator is a high-affinity ligand for the orphan G-protein-coupled receptor GPR37-Reference-Cited by-同舟云学术

The neuropeptide head activator is a high-affinity ligand for the orphan G-protein-coupled receptor GPR37

Published:2006-02-01 Issue:3 Volume:119 Page:542-549
ISSN:1477-9137
Container-title:Journal of Cell Science
language:en
Short-container-title:

Author:

Rezgaoui Meriem¹,Süsens Ute¹,Ignatov Atanas¹,Gelderblom Mathias²,Glassmeier Günter³,Franke Inga¹,Urny Jens¹,Imai Yuzuru⁴,Takahashi Ryosuke⁴,Schaller H. Chica¹

Affiliation:

1. Zentrum für Molekulare Neurobiologie Hamburg, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany

2. Klinik und Poliklinik für Neurologie, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany

3. Institut für Angewandte Physiologie, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany

4. RIKEN Brain Science Institute, Saitama 351-0198, Japan

Abstract

The neuropeptide head activator (HA) is a mitogen for mammalian cell lines of neuronal or neuroendocrine origin. HA signalling is mediated by a G-protein-coupled receptor (GPCR). Orphan GPCRs with homology to peptide receptors were screened for HA interaction. Electrophysiological recordings in frog oocytes and in mammalian cell lines as well as Ca2+ mobilisation assays revealed nanomolar affinities of HA to GPR37. HA signal transduction through GPR37 was mediated by an inhibitory G protein and required Ca2+ influx through a channel of the transient receptor potential (TRP) family. It also required activation of Ca2+-dependent calmodulin kinase and phosphoinositide 3-kinase. Respective inhibitors blocked HA signalling and HA-induced mitosis in GPR37-expressing cells. HA treatment resulted in internalisation of GPR37. Overexpression of GPR37 led to aggregate formation, retention of the receptor in the cytoplasm and low survival rates of transfected cells, confirming the notion that misfolded GPR37 contributes to cell death, as observed in Parkinson's disease.

Publisher

The Company of Biologists

Subject

Cell Biology

Link

http://journals.biologists.com/jcs/article-pdf/119/3/542/1513265/542.pdf

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