Abstract
Phosphorylation is a primary modulator of mammalian G-protein coupled receptor (GPCR) activity. The GPCR melanopsin is the photopigment of intrinsically photosensitive retinal ganglion cells (ipRGCs) in the mammalian retina. Recent evidence from in vitro experiments suggests that the G-protein coupled receptor kinase 2 (GRK2) phosphorylates melanopsin and reduces its activity following light exposure. Using an ipRGC-specific GRK2 loss-of-function mouse, we show that GRK2 loss alters melanopsin response dynamics and termination time in postnatal day 8 (P8) ipRGCs but not in older animals. However, the alterations are small in comparison to the changes reported for other opsins with loss of their cognate GRK. These results suggest GRK2 contributes to melanopsin deactivation, but that other mechanisms account for most of modulation of melanopsin activity in ipRGCs.
Highlights
Photosensitive retinal ganglion cells are photoreceptors in the mammalian retina which mediate photic entrainment of circadian rhythms and control the pupillary light response [1]
GRK2flox mice were bred with a line of C57BL/6, 129SvJ mixed background mice containing a Cre-recombinase gene knocked into the melanopsin locus (Gift of Samer Hattar, [13])
In GRKflox/flox;Opn4Cre postnatal day 8 (P8) cells, peak firing was unchanged from controls (Fig 1), indicating the ability of cells to fire was intact in animals lacking G-protein coupled receptor kinase 2 (GRK2) activity in Intrinsically photosensitive retinal ganglion cells (ipRGCs)
Summary
Photosensitive retinal ganglion cells (ipRGCs) are photoreceptors in the mammalian retina which mediate photic entrainment of circadian rhythms and control the pupillary light response [1]. These cells use melanopsin (Opn4) as their intrinsic photopigment [2, 3]. IpRGCs exhibit adaptation changes, including desensitization under continuous background light, ‘resensitization’ to flashes of light during the decaying phase of a continuous light response, acceleration of light responses under continuous illumination, and recovery from desensitization upon extended dark incubation [4]. Do and Yao [5] have shown that ipRGC responses follow a Weber-Fechner-like relation [6] upon exposure to increasing background light levels similar to rods and cones.
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