Sustained Melanopsin Photoresponse Is Supported by Specific Roles of β-Arrestin 1 and 2 in Deactivation and Regeneration of Photopigment.

ABSTRACT: 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 β-arrestin 1 (βARR1) and β-arrestin 2. β-arrestin 2 primarily regulates the deactivation of melanopsin; accordingly, βαrr2^-/- mice exhibit prolonged ipRGC responses after cessation of a light pulse. β-arrestin 1 primes melanopsin for regeneration. Therefore, βαrr1^-/- ipRGCs become desensitized af

SUBMITTER: Mure LS 

PROVIDER: S-EPMC6396282 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature