Endoplasmic reticulum export of adrenergic and angiotensin II receptors is differentially regulated by Sar1 GTPase.
The molecular mechanism underlying the export of G protein-coupled receptors (GPCRs) from the endoplasmic reticulum (ER) remains largely unknown. In this manuscript, we investigated the role of Sar1 GTPase, which coordinates the assembly and budding of COPII-coated vesicles, in the cell-surface targeting, signaling and ER export of alpha(2B)-adrenergic (alpha(2B)-AR), beta(2)-AR and angiotensin II type 1 receptors (AT1R). The cell-surface expression of alpha(2B)-AR, beta(2)-AR and AT1R, and receptor-mediated ERK1/2 activation were significantly attenuated by the GTP-bound mutant Sar1H79G, suggesting that export from the ER of these receptors is mediated through the Sar1-dependent COPII-coated vesicles. Interestingly, subcellular distribution analyses showed that alpha(2B)-AR and AT1R were highly concentrated at discrete locations near the nucleus in cells expressing Sar1H79G, whereas beta(2)-AR exhibited an ER distribution. These data indicate that Sar1-catalyzed efficient GTP hydrolysis differentially regulates ER export of adrenergic and angiotensin II receptors. These data provide the first evidence indicating distinct mechanisms for the recruitment of different GPCRs into the COPII vesicles on the ER membrane.
Dong
Chunmin
C
Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, 1901 Perdido St., New Orleans, LA 70112, United States.
Zhou
Fuguo
F
Fugetta
Erin K
EK
Filipeanu
Catalin M
CM
Wu
Guangyu
G
D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000737:chemistry / Q000201:enzymology* / Q000378:metabolism; D006801:Humans; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D021381:Protein Transport; D044140:Receptor, Angiotensin, Type 1 / Q000032:analysis / Q000378:metabolism*; D011941:Receptors, Adrenergic / Q000378:metabolism*; D018341:Receptors, Adrenergic, alpha-2 / Q000032:analysis / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000032:analysis / Q000378:metabolism; D015398:Signal Transduction
C547771:ADRA2B protein, human; D044140:Receptor, Angiotensin, Type 1; D011941:Receptors, Adrenergic; D018341:Receptors, Adrenergic, alpha-2; D018343:Receptors, Adrenergic, beta-2; C493083:SAR1A protein, human; D020559:Monomeric GTP-Binding Proteins