Function of non-visual arrestins in signaling and endocytosis of the gastrin-releasing peptide receptor (GRP receptor)

Biochemical Pharmacology
Michael SchumannRobert T Jensen

Abstract

Little is known about the role of arrestins in gastrointestinal hormone/neurotransmitter receptor endocytosis. With other G protein-coupled receptors, arrestins induce G protein-uncoupling and receptor endocytosis. In this study, we used arrestin wild-type and dominant-negative mutant constructs to analyze the arrestin dependence of endocytosis and desensitization of the gastrin-releasing peptide receptor (GRP-R). Co-expression of the GRP-R with wild-type arrestin2 and arrestin3 increased not only GRP-R endocytosis but also GRP-R desensitization in arrestin-overexpressing cells. Co-expression of the dominant-negative mutants V53D-arrestin2 or V54D-arrestin3 reduced GRP-R endocytosis. Notably, different trafficking routes for agonist-activated GRP-R-arrestin2 and GRP-R-arrestin3 complexes were found. Arrestin3 internalizes with GRP-R to intracellular vesicles, arrestin2 splits from the GRP-R and localizes to the cell membrane. Also, the recycling pathway of the GRP-R was different if co-expressed with arrestin2 or arrestin3. Using different GRP-R mutants, the C-terminus and the 2nd intracellular loop of the GRP-R were found to be important for the GRP-R-arrestin interaction and for the difference in GRP receptor trafficking with...Continue Reading

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Citations

May 16, 2015·Peptides·Irene Ramos-ÁlvarezRobert T Jensen
Dec 30, 2014·Biochemical and Biophysical Research Communications·Youngjoo YunKa Young Chung
Jul 16, 2014·Bioconjugate Chemistry·Dhananjay SureshRaghuraman Kannan
Mar 27, 2012·Bioconjugate Chemistry·Mouldy Sioud, Anne Mobergslien

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