14-3-3 signal adaptor and scaffold proteins mediate GPCR trafficking
| Autor: | Haifeng Eishingdrelo, Sathapana Kongsamut, Luwa Yuan, Shahar Barbash, Alex Eishingdrelo, Thomas P. Sakmar |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Scaffold protein lcsh:Medicine Plasma protein binding Endocytosis Article Receptors G-Protein-Coupled Cell membrane 03 medical and health sciences 0302 clinical medicine medicine Animals Humans lcsh:Science Receptor beta-Arrestins G protein-coupled receptor Protein translocation Multidisciplinary Assay systems Chemistry lcsh:R Cell biology Transport protein Protein Transport 030104 developmental biology medicine.anatomical_structure 14-3-3 Proteins lcsh:Q Signal transduction hormones hormone substitutes and hormone antagonists 030217 neurology & neurosurgery Protein Binding Signal Transduction |
| Zdroj: | Scientific Reports, Vol 9, Iss 1, Pp 1-13 (2019) Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-019-47478-w |
| Popis: | Receptor trafficking is pivotal for the temporal and spatial control of GPCR signaling and is regulated by multiple cellular proteins. We provide evidence that GPCRs interact with 14-3-3 signal adaptor/scaffold proteins and that this interaction regulates receptor trafficking in two ways. We found GPCR/14-3-3 interaction signals can be agonist-induced or agonist-inhibited. Some GPCRs associate with 14-3-3 proteins at the cell membrane and agonist treatments result in disrupted GPCR/14-3-3 interaction signals. The diminished GPCR/14-3-3 interaction signals are temporally correlated with increased GPCR/β-arrestin interaction signals in response to agonist treatment. Other GPCRs showed agonist-induced GPCR/14-3-3 interaction signal increases that occur later than agonist-induced GPCR/β-arrestin interaction signals, indicating that GPCR/14-3-3 interaction occurred after receptor endocytosis. These two types of GPCR/14-3-3 interaction patterns correlate with different receptor trafficking patterns. In addition, the bioinformatic analysis predicts that approximately 90% of GPCRs contain at least one putative 14-3-3 binding motif, suggesting GPCR/14-3-3 association could be a general phenomenon. Based on these results and collective evidence, we propose a working model whereby 14-3-3 serves as a sorting factor to regulate receptor trafficking. |
| Databáze: | OpenAIRE |
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