The signal peptide of the rat corticotropin-releasing factor receptor 1 promotes receptor expression but is not essential for establishing a functional receptor

Item Type:	Article
Title:	The signal peptide of the rat corticotropin-releasing factor receptor 1 promotes receptor expression but is not essential for establishing a functional receptor
Creators Name:	Alken, M. and Rutz, C. and Koechl, R. and Donalies, U. and Oueslati, M. and Furkert, J. and Wietfeld, D. and Hermosilla, R. and Scholz, A. and Beyermann, M. and Rosenthal, W. and Schuelein, R.
Abstract:	Approximately 5-10% of the GPCRs (G-protein-coupled receptors) contain N-terminal signal peptides that are cleaved off during receptor insertion into the ER (endoplasmic reticulum) membrane by the signal peptidases of the ER. The reason as to why only a subset of GPCRs requires these additional signal peptides is not known. We have recently shown that the signal peptide of the human ET(B)-R (endothelin B receptor) does not influence receptor expression but is necessary for the translocation of the receptor's N-tail across the ER membrane and thus for the establishment of a functional receptor [Köchl, Alken, Rutz, Krause, Oksche, Rosenthal and Schülein (2002) J. Biol. Chem. 277, 16131-16138]. In the present study, we show that the signal peptide of the rat CRF-R1 (corticotropin-releasing factor receptor 1) has a different function: a mutant of the CRF-R1 lacking the signal peptide was functional and displayed wild-type properties with respect to ligand binding and activation of adenylate cyclase. However, immunoblot analysis and confocal laser scanning microscopy revealed that the mutant receptor was expressed at 10-fold lower levels than the wild-type receptor. Northern-blot and in vitro transcription translation analyses precluded the possibility that the reduced receptor expression is due to decreased transcription or translation levels. Thus the signal peptide of the CRF-R1 promotes an early step of receptor biogenesis, such as targeting of the nascent chain to the ER membrane and/or the gating of the protein-conducting translocon of the ER membrane.
Keywords:	Corticotropin-releasing factor receptor 1 (CRF-R1), Endoplasmic reticulum, Functional receptor, G-protein-coupled receptor (GPCR), Signal peptide, Translocon, Animals, Rats
Source:	Biochemical Journal
ISSN:	0264-6021
Publisher:	Portland Press
Volume:	390
Number:	Pt 2
Page Range:	455-464
Date:	2005
Official Publication:	https://doi.org/10.1042/BJ20050113
PubMed:	View item in PubMed

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