The pseudo signal peptide of the corticotropin-releasing factor receptor type 2a decreases receptor expression and prevents Gi-mediated inhibition of adenylyl cyclase activity

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Item Type:	Article
Title:	The pseudo signal peptide of the corticotropin-releasing factor receptor type 2a decreases receptor expression and prevents Gi-mediated inhibition of adenylyl cyclase activity
Creators Name:	Schulz, K., Rutz, C., Westendorf, C., Ridelis, I., Vogelbein, S., Furkert, J., Schmidt, A., Wiesner, B. and Schuelein, R.
Abstract:	The corticotropin-releasing factor receptor type 2a (CRF(2(a))R) belongs to the family of G protein-coupled receptors. The receptor possesses an N-terminal pseudo signal peptide that is unable to mediate targeting of the nascent chain to the endoplasmic reticulum membrane during early receptor biogenesis. The pseudo signal peptide remains uncleaved and consequently forms an additional hydrophobic receptor domain with unknown function that is unique within the large G protein-coupled receptor protein family. Here, we have analyzed the functional significance of this domain in comparison with the conventional signal peptide of the homologous corticotropin-releasing factor receptor type 1 (CRF(1)R). We show that the presence of the pseudo signal peptide leads to a very low cell surface receptor expression of the CRF(2(a))R in comparison with the CRF(1)R. Moreover, whereas the presence of the pseudo signal peptide did not affect coupling to the G(s) protein, G(i)-mediated inhibition of adenylyl cyclase activity was abolished. The properties mediated by the pseudo signal peptide were entirely transferable to the CRF(1)R in signal peptide exchange experiments. Taken together, our results show that signal peptides do not only influence early protein biogenesis. In the case of the corticotropin-releasing factor receptor subtypes, the use of conventional and pseudo signal peptides have an unexpected influence on signal transduction.
Keywords:	G Protein-coupled Receptors (GPCR), G Proteins, Protein Processing, Protein Targeting, Signal Peptidase, Signal Transduction, Corticotropin-Releasing Factor Receptor, Animals, Rats
Source:	Journal of Biological Chemistry
ISSN:	0021-9258
Publisher:	American Society for Biochemistry and Molecular Biology
Volume:	285
Number:	43
Page Range:	32878-32887
Date:	22 October 2010
Official Publication:	https://doi.org/10.1074/jbc.M110.129627
PubMed:	View item in PubMed

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