| First Author | George K | Year | 2024 |
| Journal | iScience | Volume | 27 |
| Issue | 6 | Pages | 110047 |
| PubMed ID | 38883814 | Mgi Jnum | J:349923 |
| Mgi Id | MGI:7660136 | Doi | 10.1016/j.isci.2024.110047 |
| Citation | George K, et al. (2024) Robust GRK2/3/6-dependent desensitization of oxytocin receptor in neurons. iScience 27(6):110047 |
| abstractText | Oxytocin plays critical roles in the brain as a neuromodulator, regulating social and other affective behavior. However, the regulatory mechanisms controlling oxytocin receptor (OXTR) signaling in neurons remain unexplored. In this study, we have identified robust and rapid-onset desensitization of OXTR response in multiple regions of the mouse brain. Both cell autonomous spiking response and presynaptic activation undergo similar agonist-induced desensitization. G-protein-coupled receptor kinases (GRK) GRK2, GRK3, and GRK6 are recruited to the activated OXTR in neurons, followed by recruitment of beta-arrestin-1 and -2. Neuronal OXTR desensitization was impaired by suppression of GRK2/3/6 kinase activity but remained unaltered with double knockout of beta-arrestin-1 and -2. Additionally, we observed robust agonist-induced internalization of neuronal OXTR and its Rab5-dependent recruitment to early endosomes, which was impaired by GRK2/3/6 inhibition. This work defines distinctive aspects of the mechanisms governing OXTR desensitization and internalization in neurons compared to prior studies in heterologous cells. |
