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The α-Arrestin ARRDC3 Regulates the Endosomal Residence Time and Intracellular Signaling of the β2-Adrenergic Receptor
| Content Provider | Scilit |
|---|---|
| Author | Tian, Xufan Irannejad, Roshanak Bowman, Shanna L. Du, Yang Puthenveedu, Manojkumar A. von Zastrow, Mark Benovic, Jeffrey L. |
| Copyright Year | 2016 |
| Description | Journal: Journal of Biological Chemistry Arrestin domain-containing protein 3 (ARRDC3) is a member of the mammalian α-arrestin family, which is predicted to share similar tertiary structure with visual-/β-arrestins and also contains C-terminal PPXY motifs that mediate interaction with E3 ubiquitin ligases. Recently, ARRDC3 has been proposed to play a role in regulating the trafficking of G protein-coupled receptors, although mechanistic insight into this process is lacking. Here, we focused on characterizing the role of ARRDC3 in regulating the trafficking of the $β_{2}$-adrenergic receptor $(β_{2}$AR). We find that ARRDC3 primarily localizes to EEA1-positive early endosomes and directly interacts with the $β_{2}$AR in a ligand-independent manner. Although ARRDC3 has no effect on $β_{2}$AR endocytosis or degradation, it negatively regulates $β_{2}$AR entry into SNX27-occupied endosomal tubules. This results in delayed recycling of the receptor and a concomitant increase in $β_{2}$AR-dependent endosomal signaling. Thus, ARRDC3 functions as a switch to modulate the endosomal residence time and subsequent intracellular signaling of the $β_{2}$AR. |
| Related Links | http://www.jbc.org/content/291/28/14510.full.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4938174/pdf http://www.jbc.org/article/S0021925820349115/pdf |
| Ending Page | 14525 |
| Page Count | 16 |
| Starting Page | 14510 |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| DOI | 10.1074/jbc.m116.716589 |
| Journal | Journal of Biological Chemistry |
| Issue Number | 28 |
| Volume Number | 291 |
| Language | English |
| Publisher | Elsevier BV |
| Publisher Date | 2016-07-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Journal of Biological Chemistry G Protein-coupled Receptor (gpcr) Arrestin Domain-containing Protein 3 Endosomal Signaling Receptor Recycling Β2 Adrenergic Receptor |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
