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Cell Rep. 2018 Nov 27;25(9):2497-2509.e4. doi: 10.1016/j.celrep.2018.11.008.

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

Author information

1
Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
2
Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA; Keio University School of Medicine, Tokyo, Japan.
3
St. Olaf College, 1520 St. Olaf Avenue, Northfield, MN 55057, USA.
4
Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address: satchin@salk.edu.

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 after repeated or prolonged photostimulation. The lack of either β-arrestin attenuates ipRGC response under prolonged illumination, suggesting that β-arrestin 2-mediated deactivation and β-arrestin 1-dependent regeneration of melanopsin function in sequence. In conclusion, we discovered a molecular mechanism by which β-arrestins regulate different aspects of melanopsin photoresponses and allow ipRGC-sustained responses under prolonged illumination.

KEYWORDS:

beta arrestin; melanopsin; non-visual responses to light; photophobia; pupillary reflex; retina; retinal ganglion cell

PMID:
30485815
DOI:
10.1016/j.celrep.2018.11.008
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