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Regulation of the cell surface traffic of α 2 ‐adrenergic receptors by small GTPases
Author(s) -
Zhu Shu,
Li Chunman,
Wu Guangyu
Publication year - 2012
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.26.1_supplement.837.6
Subject(s) - gtpase , rab , microbiology and biotechnology , intracellular , g protein coupled receptor , receptor , small gtpase , cell , chemistry , mutant , biology , signal transduction , biochemistry , gene
The molecular mechanisms responsible for the cell surface targeting of nascent G protein‐coupled receptors (GPCRS) remain poorly elucidated. Our previous studies have utilized α 2B ‐adrenergic receptor (AR) as a model to define the pathways that mediate forward transport of GPCRs by studying the function of small GTPases in the Rab and ARF/Sar1 subfamilies. In this study, we compared the small GTPases‐coordinated cell surface movement of three α 2 ‐ARs and investigated the possible mechanisms. Transient expression of dominant‐negative mutants of Rab, ARF, and Sar1 clearly inhibited the cell surface transport of α 2A ‐AR and α 2C ‐AR. Although the cell surface expression of α 2A ‐AR was much more abundant than that of α 2C ‐AR, their responsiveness to the small GTPase mutants was similar. In contrast, the cell surface transport of α 2B ‐AR was inhibited by some, but not all the mutants. More interestingly, three α 2 ‐ARs differentially interacted with some small GTPases and the interaction was identified to be mediated via the third intracellular loops and/or the C‐terminal tails of the receptors. These data have demonstrated that the cell surface traffic of three α 2 ‐ARs is controlled by different mechanisms and their differential interactions with different small GTPases involved in distinct transport steps along the secretory pathway may play an important role.