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Journal article
Guanylate cyclase-activating protein 2 contributes to phototransduction and light adaptation in mouse cone photoreceptors
The Journal of biological chemistry, v 293(19), pp 7457-7465
11 May 2018
PMID: 29549122
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Light adaptation of photoreceptor cells is mediated by Ca2+-dependent mechanisms. In darkness, Ca2+ influx through cGMP-gated channels into the outer segment of photoreceptors is balanced by Ca2+ extrusion via Na+/Ca2+, K+ exchangers (NCKXs). Light activates a G protein signaling cascade, which closes cGMP-gated channels and decreases Ca2+ levels in photoreceptor outer segment because of continuing Ca2+ extrusion by NCKXs. Guanylate cyclase-activating proteins (GCAPs) then up-regulate cGMP synthesis by activating retinal membrane guanylate cyclases (RetGCs) in low Ca2+. This activation of RetGC accelerates photoresponse recovery and critically contributes to light adaptation of the nighttime rod and daytime cone photoreceptors. In mouse rod photoreceptors, GCAP1 and GCAP2 both contribute to the Ca2+-feedback mechanism. In contrast, only GCAP1 appears to modulate RetGC activity in mouse cones because evidence of GCAP2 expression in cones is lacking. Surprisingly, we found that GCAP2 is expressed in cones and can regulate light sensitivity and response kinetics as well as light adaptation of GCAP1-deficient mouse cones. Furthermore, we show that GCAP2 promotes cGMP synthesis and cGMP-gated channel opening in mouse cones exposed to low Ca2+. Our biochemical model and experiments indicate that GCAP2 significantly contributes to the activation of RetGC1 at low Ca2+ when GCAP1 is not present. Of note, in WT mouse cones, GCAP1 dominates the regulation of cGMP synthesis. We conclude that, under normal physiological conditions, GCAP1 dominates the regulation of cGMP synthesis in mouse cones, but if its function becomes compromised, GCAP2 contributes to the regulation of phototransduction and light adaptation of cones.
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Details
- Title
- Guanylate cyclase-activating protein 2 contributes to phototransduction and light adaptation in mouse cone photoreceptors
- Creators
- Frans Vinberg - College Station Medical CenterIgor V. Peshenko - Salus UniversityJeannie Chen - University of Southern CaliforniaAlexander M. Dizhoor - Salus UniversityVladimir J. Kefalov - College Station Medical Center
- Publication Details
- The Journal of biological chemistry, v 293(19), pp 7457-7465
- Publisher
- Amer Soc Biochemistry Molecular Biology Inc
- Number of pages
- 9
- Grant note
- Ella and Georg Ehrnrooth Foundation EY026651; EY019312; EY027387; EY012155; EY027193; EY011522; EY02687 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Research to Prevent Blindness; Research to Prevent Blindness (RPB) R00EY026651 / NATIONAL EYE INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Eye Institute (NEI)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy; Pennsylvania College of Optometry (PCO)
- Web of Science ID
- WOS:000432174500036
- Scopus ID
- 2-s2.0-85046946091
- Other Identifier
- 991022035115704721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology