| First Author | Mure LS | Year | 2018 |
| Journal | Cell Rep | Volume | 25 |
| Issue | 9 | Pages | 2497-2509.e4 |
| PubMed ID | 30485815 | Mgi Jnum | J:270672 |
| Mgi Id | MGI:6278603 | Doi | 10.1016/j.celrep.2018.11.008 |
| Citation | Mure LS, et al. (2018) Sustained Melanopsin Photoresponse Is Supported by Specific Roles of beta-Arrestin 1 and 2 in Deactivation and Regeneration of Photopigment. Cell Rep 25(9):2497-2509.e4 |
| abstractText | Melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) are indispensable for non-image-forming visual responses that sustain under prolonged illumination. For sustained signaling of ipRGCs, the melanopsin photopigment must continuously regenerate. The underlying mechanism is unknown. We discovered that a cluster of Ser/Thr sites within the C-terminal region of mammalian melanopsin is phosphorylated after a light pulse. This forms a binding site for beta-arrestin 1 (betaARR1) and beta-arrestin 2. beta-arrestin 2 primarily regulates the deactivation of melanopsin; accordingly, betaalpharr2(-/-) mice exhibit prolonged ipRGC responses after cessation of a light pulse. beta-arrestin 1 primes melanopsin for regeneration. Therefore, betaalpharr1(-/-) ipRGCs become desensitized after repeated or prolonged photostimulation. The lack of either beta-arrestin attenuates ipRGC response under prolonged illumination, suggesting that beta-arrestin 2-mediated deactivation and beta-arrestin 1-dependent regeneration of melanopsin function in sequence. In conclusion, we discovered a molecular mechanism by which beta-arrestins regulate different aspects of melanopsin photoresponses and allow ipRGC-sustained responses under prolonged illumination. |
