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

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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., Rutz, C., Koechl, R., Donalies, U., Oueslati, M., Furkert, J., Wietfeld, D., Hermosilla, R., Scholz, A., Beyermann, M., 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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