Regulation of Mammalian Cone Phototransduction by Recoverin and Rhodopsin Kinase

Abstract

Background: Calcium-mediated feedback to phototransduction is critical for modulating cone responses under different lighting conditions. Results: The calcium-binding protein recoverin potentiates dim light sensitivity, whereas increasing expression of its target, GRK1, delays response shutoff in cones. Conclusion: Recoverin and GRK1 levels modulate cone phototransduction. Significance: Cone pigment inactivation regulates cone responses in dim light but not in bright light.

Evolutionary signatures of photoreceptor transmutation in geckos reveal potential adaptation and convergence with snakes

“…; Sakurai et al. ), and thus an elevated recoverin concentration could contribute to a more rod‐like physiology of gecko cones.…”

“…Interestingly, we found recoverin (RCVRN) expression to be relatively higher in G. gecko than A. carolinensis, but a lack of replicates prevents a more detailed, quantitative comparison. In addition to its role in recovery of the light response and regulating rhodopsin kinase, recoverin may act to increase the sensitivity of the light response in cones under dimlight conditions, when calcium levels are high (Gray-Keller et al 1993;Erickson et al 1998;Makino et al 2004;Sampath et al 2005;Sakurai et al 2015), and thus an elevated recoverin concentration could contribute to a more rod-like physiology of gecko cones.…”

Regulation of calcium homeostasis in the outer segments of rod and cone photoreceptors

“…As in rods, deletion of recoverin in cones was found to accelerate the response recovery in darkness and in dim background light. However, unlike the case in rods, the deletion of recoverin also caused reduction of the estimated single-photon response amplitude and decrease in cone sensitivity (Sakurai et al, 2015). Thus, by slowing pigment inactivation, recoverin in cones boosts their sensitivity in dim background light, possibly enhancing the ability of cones to detect light near threshold.…”

“…Maintenance of vision under continuous illumination and re-opening of the CNG channels after transient light stimuli require efficient inactivation of R* (Chen et al, 1995b) and the Tα-GTP-PDE complex (Chen et al, 2000), as well as restoration of cGMP levels. The activity of pigments is quenched by phosphorylations by rhodopsin kinase (GRK) (Chen et al, 1999a; Kennedy et al, 2004; Mendez et al, 2000; Mendez et al, 2001; Sakurai et al, 2015) and arrestin binding (Gurevich et al, 2011; Nikonov et al, 2008; Xu et al, 1997) whereas Tα-GTP-PDEs are deactivated by GTPase activating GAP proteins that accelerate the hydrolysis of GTP (Krispel et al, 2006). The synthesis of cGMP is achieved by retinal membrane guanylyl cyclases (RetGCs), which together with phosphodiesterase, maintain a proper cGMP homeostasis in the photoreceptor outer segments (Dizhoor et al, 1994; Koch, 1991).…”

“…Strikingly, cones, exposed to continuous illumination expected to bleach >90% of their pigment content, can retain more than 50% of their maximal dark-adapted response amplitude (Jones et al, 1993; Kenkre et al, 2005; Schnapf et al, 1990). The mechanisms that produce the difference in adaptation capacity between rods and cones are still poorly understood and are an area of active research (Sakurai et al, 2011; Sakurai et al, 2015). Adaptation in the short time scale of seconds is driven primarily by calcium-mediated feedback on their phototransduction cascades in both rods and cones (Matthews et al, 1988; Nakatani and Yau, 1988a).…”