PUBLICATION
Grk7 but not Grk1 undergoes cAMP-dependent phosphorylation in zebrafish cone photoreceptors and mediates cone photoresponse recovery to elevated cAMP
- Authors
- Chrispell, J.D., Xiong, Y., Weiss, E.R.
- ID
- ZDB-PUB-221025-3
- Date
- 2022
- Source
- The Journal of biological chemistry 298(12): 102636 (Journal)
- Registered Authors
- Chrispell, Jared, Weiss, Ellen R., Xiong, Yubin
- Keywords
- none
- MeSH Terms
-
- Animals
- G-Protein-Coupled Receptor Kinase 1/genetics
- G-Protein-Coupled Receptor Kinase 1/metabolism
- G-Protein-Coupled Receptor Kinases*/genetics
- G-Protein-Coupled Receptor Kinases*/metabolism
- Phosphorylation
- Retinal Cone Photoreceptor Cells*/metabolism
- Rhodopsin/genetics
- Rhodopsin/metabolism
- Zebrafish*/metabolism
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- PubMed
- 36273582 Full text @ J. Biol. Chem.
Citation
Chrispell, J.D., Xiong, Y., Weiss, E.R. (2022) Grk7 but not Grk1 undergoes cAMP-dependent phosphorylation in zebrafish cone photoreceptors and mediates cone photoresponse recovery to elevated cAMP. The Journal of biological chemistry. 298(12):102636.
Abstract
In the vertebrate retina, phosphorylation of photoactivated visual pigments in rods and cones by G protein-coupled receptor kinases (GRKs) is essential for sustained visual function. Previous in vitro analysis demonstrated that GRK1 and GRK7 are phosphorylated by PKA, resulting in a reduced capacity to phosphorylate rhodopsin. In vivo observations revealed that GRK phosphorylation occurs in the dark and is cAMP-dependent. In many vertebrates, including humans and zebrafish, GRK1 is expressed in both rods and cones while GRK7 is expressed only in cones. However, mice express only GRK1 in both rods and cones and lack GRK7. We recently generated a mutation in GRK1 that deletes the phosphorylation site, Ser21. This mutant demonstrated delayed dark adaptation in mouse rods but not in cones in vivo, suggesting GRK1 may serve a different role depending upon the photoreceptor cell type in which it is expressed. Here, zebrafish were selected to evaluate the role of cAMP-dependent GRK phosphorylation in cone photoreceptor recovery. ERG analyses of larvae treated with forskolin show that elevated intracellular cAMP significantly decreases recovery of the cone photoresponse, which is mediated by Grk7a rather than Grk1b. Using a cone-specific dominant negative PKA transgene, we show for the first time that PKA is required for Grk7a phosphorylation in vivo. Lastly, immunoblot analyses of rod grk1a-/- and cone grk1b-/- zebrafish and Nrl-/- mouse show that cone-expressed Grk1 does not undergo cAMP-dependent phosphorylation in vivo. These results provide a better understanding of the function of Grk phosphorylation in relation to cone adaptation and recovery.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping