» Articles » PMID: 29435986

Role of Recoverin in Rod Photoreceptor Light Adaptation

Overview
Journal J Physiol
Specialty Physiology
Date 2018 Feb 14
PMID 29435986
Citations 16
Authors
Affiliations
Soon will be listed here.
Abstract

Key Points: Recoverin is a small molecular-weight, calcium-binding protein in rod outer segments that can modulate the rate of rhodopsin phosphorylation. We describe two additional and perhaps more important functions during photoreceptor light adaptation. Recoverin influences the rate of change of adaptation. In wild-type rods, sensitivity and response integration time adapt with similar time constants of 150-200 ms. In Rv-/- rods lacking recoverin, sensitivity declines faster and integration time is already shorter and not significantly altered. During steady light exposure, rod circulating current slowly increases during a time course of tens of seconds, gradually extending the operating range of the rod. In Rv-/- rods, this mechanism is deleted, steady-state currents are already larger and rods saturate at brighter intensities. We propose that recoverin modulates spontaneous and light-activated phophodiesterase-6, the phototransduction effector enzyme, to increase sensitivity in dim light but improve responsiveness to change in brighter illumination.

Abstract: Recoverin is a small molecular-weight, calcium-binding protein in rod outer segments that binds to G-protein receptor kinase 1 and can alter the rate of rhodopsin phosphorylation. A change in phosphorylation should change the lifetime of light-activated rhodopsin and the gain of phototransduction, but deletion of recoverin has little effect on the sensitivity of rods either in the dark or in dim-to-moderate background light. We describe two additional functions perhaps of greater physiological significance. (i) When the ambient intensity increases, sensitivity and integration time decrease in wild-type (WT) rods with similar time constants of 150-200 ms. Recoverin is part of the mechanism controlling this process because, in Rv-/- rods lacking recoverin, sensitivity declines more rapidly and integration time is already shorter and not further altered. (ii) During steady light exposure, WT rod circulating current slowly increases during a time course of tens of seconds, gradually extending the operating range of the rod. In Rv-/- rods, this mechanism is also deleted, steady-state currents are already larger and rods saturate at brighter intensities. We argue that neither (i) nor (ii) can be caused by modulation of rhodopsin phosphorylation but may instead be produced by direct modulation of phophodiesterase-6 (PDE6), the phototransduction effector enzyme. We propose that recoverin in dark-adapted rods keeps the integration time long and the spontaneous PDE6 rate relatively high to improve sensitivity. In background light, the integration time is decreased to facilitate detection of change and motion and the spontaneous PDE6 rate decreases to augment the rod working range.

Citing Articles

Genetic manipulation of rod-cone differences in mouse retina.

Morshedian A, Jiang Z, Radu R, Fain G, Sampath A PLoS One. 2024; 19(5):e0300584.

PMID: 38709779 PMC: 11073714. DOI: 10.1371/journal.pone.0300584.


Inefficacy of anti-VEGF therapy reflected in VEGF-mediated photoreceptor degeneration.

Xu X, Han N, Zhao F, Fan R, Guo Q, Han X Mol Ther Nucleic Acids. 2024; 35(2):102176.

PMID: 38689803 PMC: 11059333. DOI: 10.1016/j.omtn.2024.102176.


Analysis of dim-light responses in rod and cone photoreceptors with altered calcium kinetics.

Abtout A, Reingruber J J Math Biol. 2023; 87(5):69.

PMID: 37823947 PMC: 10570263. DOI: 10.1007/s00285-023-02005-4.


Light Adaptation of Retinal Rod Bipolar Cells.

Griffis K, Fehlhaber K, Rieke F, Sampath A J Neurosci. 2023; 43(24):4379-4389.

PMID: 37208176 PMC: 10278674. DOI: 10.1523/JNEUROSCI.0444-23.2023.


Generation of an RCVRN-eGFP Reporter hiPSC Line by CRISPR/Cas9 to Monitor Photoreceptor Cell Development and Facilitate the Cell Enrichment for Transplantation.

Guan Y, Wang Y, Zheng D, Xie B, Xu P, Gao G Front Cell Dev Biol. 2022; 10:870441.

PMID: 35573687 PMC: 9096726. DOI: 10.3389/fcell.2022.870441.


References
1.
Sampath A, Strissel K, Elias R, Arshavsky V, McGinnis J, Chen J . Recoverin improves rod-mediated vision by enhancing signal transmission in the mouse retina. Neuron. 2005; 46(3):413-20. DOI: 10.1016/j.neuron.2005.04.006. View

2.
HODGKIN A, McNaughton P, Nunn B . Measurement of sodium-calcium exchange in salamander rods. J Physiol. 1987; 391:347-70. PMC: 1192218. DOI: 10.1113/jphysiol.1987.sp016742. View

3.
Kawamura S . Inhibition of rhodopsin phosphorylation by S-modulins: purification, reconstitution, and assays. Methods Enzymol. 2000; 316:3-20. DOI: 10.1016/s0076-6879(00)16713-8. View

4.
Mendez A, Burns M, Sokal I, Dizhoor A, Baehr W, Palczewski K . Role of guanylate cyclase-activating proteins (GCAPs) in setting the flash sensitivity of rod photoreceptors. Proc Natl Acad Sci U S A. 2001; 98(17):9948-53. PMC: 55558. DOI: 10.1073/pnas.171308998. View

5.
Calvert P, Govardovskii V, Arshavsky V, Makino C . Two temporal phases of light adaptation in retinal rods. J Gen Physiol. 2002; 119(2):129-45. PMC: 2233805. DOI: 10.1085/jgp.119.2.129. View