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Regulation of α 2 ‐Adrenergic Receptor Cell Surface Transport by Spliced GGA Variants
Author(s) -
Zhang Maoxiang,
Huang Wei,
Davis Jason,
Wu Guangyu
Publication year - 2016
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.30.1_supplement.1266.5
Subject(s) - endosome , microbiology and biotechnology , signal transducing adaptor protein , golgi apparatus , clathrin , receptor , transport protein , intracellular , adp ribosylation factor , cell , biology , chemistry , endocytosis , signal transduction , biochemistry , endoplasmic reticulum
Golgi‐localized, γ‐adaptin ear domain homology, ADP ribosylation factor‐binding proteins (GGAs) have been well characterized to function as adaptor proteins for clathrin‐coated vesicles and are involved in the sorting of cargo proteins at the trans‐Golgi network (TGN) into the endosomal/lysosomal pathway. We have recently reported that GGAs are involved in the anterograde transport of α 2B ‐adrenergic receptor (α 2B ‐AR), a prototypic G protein‐coupled receptor. Here we have determined the role of several highly expressed GGA variants in the cell surface targeting of α 2B ‐AR and many other cargos. We demonstrated that the naturally occurring truncated form of GGA1 (GGA1t) lacking the N‐terminal domain had normal intracellular localization and formed homodimers and heterodimers with other GGAs. Interestingly, overexpression of GGA1t inhibited the cell surface export of α 2B ‐AR and arrested the receptor in the Golgi compartment. We also found that, in marked contrast to its wild‐type counterpart, GGA1t was unable to bind to the cargo α 2B ‐AR and to recruit clathrin onto the TGN. In addition, enhanced GGA1t expression also blocked the trafficking of CI‐MPR, a well‐known cargo that transports via the GGA‐mediated pathway. These data provide evidence implicating that the truncated form of GGA1 behaviors as a dominant‐negative regulator for the cell surface export of α 2B ‐AR which is mediated via multiple mechanisms.