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PMID: 19220814 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

A single conserved leucine residue on the first intracellular loop regulates ER export of G protein-coupled receptors.

Traffic (Copenhagen, Denmark) ·Vol. 10 ·No. 5 ·2009-05-00 ·Pages 552-66

Duvernay MT, Dong C, Zhang X, Robitaille M, Hébert TE, Wu G

Abstract

The intrinsic structural determinants for export trafficking of G protein-coupled receptors (GPCRs) have been mainly identified in the termini of the receptors. In this report, we determined the role of the first intracellular loop (ICL1) in the transport from the endoplasmic reticulum (ER) to the cell surface of GPCRs. The alpha(2B)-adrenergic receptor (AR) mutant lacking the ICL1 is unable to traffic to the cell surface and to initiate signaling measured as ERK1/2 activation. Mutagenesis studies identify a single Leu48 residue in the ICL1 modulates alpha(2B)-AR export from the ER. The ER export function of the Leu48 residue can be substituted by Phe, but not Ile, Val, Tyr and Trp, and is unlikely involved in correct folding or dimerization of alpha(2B)-AR in the ER. Importantly, the isolated Leu residue is remarkably conserved in the center of the ICL1s among the family A GPCRs and is also required for the export to the cell surface of beta(2)-AR, alpha(1B)-AR and angiotensin II type 1 receptor. These data indicate a crucial role for a single Leu residue within the ICL1 in ER export of GPCRs.

MeSH Terms
Animals Biological Transport Cell Membrane/metabolism Cytoplasm/metabolism Dimerization Endoplasmic Reticulum/chemistry,metabolism Isoleucine/analysis,metabolism Leucine/analysis,metabolism Phenylalanine/analysis,metabolism Protein Transport/physiology Receptor, Angiotensin, Type 1/analysis,metabolism Receptors, Adrenergic/analysis,metabolism Receptors, G-Protein-Coupled/analysis,chemistry,metabolism Signal Transduction
Chemicals
Receptor, Angiotensin, Type 1 Receptors, Adrenergic Receptors, G-Protein-Coupled Isoleucine Phenylalanine Leucine
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Duvernay Matthew T
Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, 1901 Perdido St, New Orleans, LA 70112, USA.
Dong Chunmin
Zhang Xiaoping
Robitaille Mélanie
Hébert Terence E
Wu Guangyu
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Article Info
Journal
Traffic (Copenhagen, Denmark)
Abbr.
Traffic
ISSN
1600-0854
DOI
10.1111/j.1600-0854.2009.00890.x
Published
2009-05-00
Epub
2009-00-11
Pages
552-66
Language
English
Region
England
NLM ID
100939340
PMCID
PMC2852481
Subset
IM
Grants
CIHR · Canada
NIGMS NIH HHS · R01GM076167 · United States
NIGMS NIH HHS · R01 GM076167-03 · United States
NCRR NIH HHS · P20 RR018766 · United States
NCRR NIH HHS · P20RR018766 · United States
NIGMS NIH HHS · R01 GM076167 · United States
External Links
PubMed source DOI: 10.1111/j.1600-0854.2009.00890.x PMC Full Text View journal details
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