PMID- 17716866 OWN - NLM STAT- MEDLINE DCOM- 20071113 LR - 20181113 IS - 0898-6568 (Print) IS - 0898-6568 (Linking) VI - 19 IP - 11 DP - 2007 Nov TI - Regulation of anterograde transport of adrenergic and angiotensin II receptors by Rab2 and Rab6 GTPases. PG - 2388-99 AB - Three Rab GTPases, Rab1, Rab2 and Rab6, are involved in protein transport between the endoplasmic reticulum (ER) and the Golgi. Whereas Rab1 regulates the anterograde ER-to-Golgi transport, Rab2 and Rab6 coordinate the retrograde Golgi-to-ER transport. We have previously demonstrated that Rab1 differentially modulates the export trafficking of distinct G protein-coupled receptors (GPCRs). In this report, we determined the role of Rab2 and Rab6 in the cell-surface expression and signaling of alpha(2B)-adrenergic (alpha(2B)-AR), beta(2)-AR and angiotensin II type 1 receptors (AT1R). Expression of the GTP-bound mutant Rab2Q65L significantly attenuated the cell-surface expression of both alpha(2B)-AR and beta(2)-AR, whereas the GTP-bound mutant Rab6Q72L selectively inhibited the transport of beta(2)-AR, but not alpha(2B)-AR. Similar results were obtained by siRNA-mediated selective knockdown of endogenous Rab2 and Rab6. Consistently, Rab2Q65L and Rab2 siRNA inhibited alpha(2B)-AR and beta(2)-AR signaling measured as ERK1/2 activation and cAMP production, respectively, whereas Rab6Q72L and Rab6 siRNA reduced signaling of beta(2)-AR, but not alpha(2B)-AR. Similar to the beta(2)-AR, AT1R expression at the cell surface and AT1R-promoted inositol phosphate accumulation were inhibited by Rab6Q72L. Furthermore, the nucleotide-free mutant Rab6N126I selectively attenuated the cell-surface expression of beta(2)-AR and AT1R, but not alpha(2B)-AR. These data demonstrate that Rab2 and Rab6 differentially influence anterograde transport and signaling of GPCRs. These data also provide the first evidence indicating that Rab6-coordinated retrograde transport selectively modulates intracellular trafficking and signaling of GPCRs. FAU - Dong, Chunmin AU - Dong C AD - Department of Pharmacology and Experimental Therapeutics, Louisiana State University, Health Sciences Center, New Orleans, LA 70112, USA. FAU - Wu, Guangyu AU - Wu G LA - eng GR - R01 GM076167/GM/NIGMS NIH HHS/United States GR - R01 GM076167-02/GM/NIGMS NIH HHS/United States GR - GM076167/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20070801 PL - England TA - Cell Signal JT - Cellular signalling JID - 8904683 RN - 0 (Mutant Proteins) RN - 0 (RNA, Small Interfering) RN - 0 (Rab6 protein) RN - 0 (Receptor, Angiotensin, Type 1) RN - 0 (Receptors, Adrenergic, alpha-2) RN - 0 (Receptors, Adrenergic, beta-2) RN - 0 (Receptors, G-Protein-Coupled) RN - 0RH81L854J (Glutamine) RN - EC 3.6.5.2 (rab GTP-Binding Proteins) RN - EC 3.6.5.2 (rab2 GTP-Binding Protein) RN - K3Z4F929H6 (Lysine) SB - IM MH - Animals MH - Cell Line MH - Genes, Dominant MH - Glutamine/genetics MH - Humans MH - Lysine/genetics MH - Mutant Proteins/metabolism MH - Protein Transport MH - RNA, Small Interfering/metabolism MH - Rats MH - Receptor, Angiotensin, Type 1/metabolism MH - Receptors, Adrenergic, alpha-2/metabolism MH - Receptors, Adrenergic, beta-2/metabolism MH - Receptors, G-Protein-Coupled/*metabolism MH - Signal Transduction MH - Subcellular Fractions/metabolism MH - rab GTP-Binding Proteins/*metabolism MH - rab2 GTP-Binding Protein/*metabolism PMC - PMC2072516 MID - NIHMS30930 EDAT- 2007/08/25 09:00 MHDA- 2007/11/14 09:00 PMCR- 2008/11/01 CRDT- 2007/08/25 09:00 PHST- 2007/07/06 00:00 [received] PHST- 2007/07/23 00:00 [accepted] PHST- 2007/08/25 09:00 [pubmed] PHST- 2007/11/14 09:00 [medline] PHST- 2007/08/25 09:00 [entrez] PHST- 2008/11/01 00:00 [pmc-release] AID - S0898-6568(07)00234-3 [pii] AID - 10.1016/j.cellsig.2007.07.017 [doi] PST - ppublish SO - Cell Signal. 2007 Nov;19(11):2388-99. doi: 10.1016/j.cellsig.2007.07.017. Epub 2007 Aug 1.