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The diacidic ExD motif controls angiotensin II type 2 receptor export from the endoplasmic reticulum
Author(s) -
Zhang Xiaoping,
Wu Guangyu
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.585.10
Subject(s) - endoplasmic reticulum , microbiology and biotechnology , receptor , angiotensin ii , hek 293 cells , alanine , transmembrane domain , chemistry , intracellular , mutant , biology , biochemistry , gene , amino acid
The physiological function of angiotensin II (Ang II) is mediated through the Ang II type 1 (AT1R) and type 2 receptor (AT2R), which belong to the superfamily of seven transmembrane cell surface receptors coupled to heterotrimeric G proteins. We have recently demonstrated that AT1R exit from the endoplasmic reticulum (ER) is directed by highly conserved single L residue in the first intracellular loop and F(x) 6 LL motif in the C‐terminus. In contrast, the structural determinants for angiotensin II type 2 receptor (AT2R) export trafficking remain undefined. In this study, we have demonstrated that the AT2R mutant lacking the entire C‐terminus was unable to transport to the cell surface. Progressive deletion of the C‐terminus and alanine‐scanning mutagenesis identified two acidic residues, E357 and D359, in the C‐terminus, which are required for AT2R exit out of the ER and transport to the cell surface. Mutation of E357 to A or D, D359 to A or E, ExD to AxA, and ExD to DxE significantly attenuated AT2R transport from the ER to the cell surface in HEK293 and PC12 cells. The mutated AT2R tagged with either GFP or HA was extensively localized within the ER. In contrast, these mutations and deletions did not alter total AT2R expression. These data demonstrate that the diacidic ExD motif plays an important role in modulating export trafficking of newly synthesized AT2R from the ER to the cell surface (R01GM076167).