Thomsen, Alex R.B. ; Plouffe, Bianca ; Cahill, Thomas J. ; Shukla, Arun K. ; Tarrasch, Jeffrey T. ; Dosey, Annie M. ; Kahsai, Alem W. ; Strachan, Ryan T. ; Pani, Biswaranjan ; Mahoney, Jacob P. ; Huang, Liyin ; Breton, Billy ; Heydenreich, Franziska M. ; Sunahara, Roger K. ; Skiniotis, Georgios ; Bouvier, Michel ; Lefkowitz, Robert J. (2016) GPCR-G Protein-β-Arrestin Super-Complex Mediates Sustained G Protein Signaling Cell, 166 (4). pp. 907-919. ISSN 00928674
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Official URL: http://doi.org/10.1016/j.cell.2016.07.004
Related URL: http://dx.doi.org/10.1016/j.cell.2016.07.004
Abstract
Classically, G protein-coupled receptor (GPCR) stimulation promotes G protein signaling at the plasma membrane, followed by rapid β-arrestin-mediated desensitization and receptor internalization into endosomes. However, it has been demonstrated that some GPCRs activate G proteins from within internalized cellular compartments, resulting in sustained signaling. We have used a variety of biochemical, biophysical, and cell-based methods to demonstrate the existence, functionality, and architecture of internalized receptor complexes composed of a single GPCR, β-arrestin, and G protein. These super-complexes or "megaplexes" more readily form at receptors that interact strongly with β-arrestins via a C-terminal tail containing clusters of serine/threonine phosphorylation sites. Single-particle electron microscopy analysis of negative-stained purified megaplexes reveals that a single receptor simultaneously binds through its core region with G protein and through its phosphorylated C-terminal tail with β-arrestin. The formation of such megaplexes provides a potential physical basis for the newly appreciated sustained G protein signaling from internalized GPCRs.
Item Type: | Article |
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Source: | Copyright of this article belongs to Elsevier Inc. |
ID Code: | 126449 |
Deposited On: | 13 Oct 2022 06:04 |
Last Modified: | 13 Oct 2022 06:04 |
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