TY - JOUR
T1 - Endoplasmic reticulum export of adrenergic and angiotensin II receptors is differentially regulated by Sar1 GTPase
AU - Dong, Chunmin
AU - Zhou, Fuguo
AU - Fugetta, Erin K.
AU - Filipeanu, Catalin M.
AU - Wu, Guangyu
N1 - Funding Information:
This work was supported by the National Institutes of Health grant GM076167 (to G. W.) and an American Heart Association, Southeast Affiliate postdoctoral fellowship (to C. D.). We are grateful to Drs. Stephen M. Lanier, William E. Balch, Kenneth E. Bernstein and John D. Hildebrandt for sharing reagents.
PY - 2008/6
Y1 - 2008/6
N2 - 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 α2B-adrenergic (α2B-AR), β2-AR and angiotensin II type 1 receptors (AT1R). The cell-surface expression of α2B-AR, β2-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 α2B-AR and AT1R were highly concentrated at discrete locations near the nucleus in cells expressing Sar1H79G, whereas β2-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.
AB - 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 α2B-adrenergic (α2B-AR), β2-AR and angiotensin II type 1 receptors (AT1R). The cell-surface expression of α2B-AR, β2-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 α2B-AR and AT1R were highly concentrated at discrete locations near the nucleus in cells expressing Sar1H79G, whereas β2-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.
KW - Adrenergic receptor
KW - Angiotensin II receptor
KW - Endoplasmic reticulum
KW - Export trafficking
KW - G protein-coupled receptor
KW - Sar1
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U2 - 10.1016/j.cellsig.2008.01.014
DO - 10.1016/j.cellsig.2008.01.014
M3 - Article
C2 - 18378118
AN - SCOPUS:42249108848
SN - 0898-6568
VL - 20
SP - 1035
EP - 1043
JO - Cellular Signalling
JF - Cellular Signalling
IS - 6
ER -