https://openresearch-repository.anu.edu.au/bitstream/1885/84715/2/01_Lamb_Evolution_of_2013.pdf

Evolution of phototransduction, vertebrate photoreceptors and retina.

The importance of G protein-coupled receptor (GPCR) kinases (GRKs) as regulators of GPCR signaling has been widely recognized. In humans, GRKs constitute a family of seven protein kinases involved in the phosphorylation and desensitization of agonist-activated GPCRs in many physiological processes. The GPCR desensitization process is initiated by GRKs, but involves several subsequent steps including arrestin capping of phosphorylated receptors. High-resolution crystal structures were determined for four members of the GRK family, i.e., GRK1, GRK2, GRK5, and GRK6. This allowed decoding of the molecular basis of GRK activation and interactions with GPCR substrates, as well as the GRK interactions with cellular membranes and inhibitors. Here, we focused on retinal GRKs, or photopigment kinases, rhodopsin kinase (GRK1), and GRK7, in the context of major general advances in the GRK fi eld.

G Protein-Coupled Receptor Kinases

https://repository.kulib.kyoto-u.ac.jp/dspace/bitstream/2433/187363/1/j.bbabio.2013.08.009.pdf

Cone visual pigments.

Vertebrates acquired dim-light vision when an ancestral cone evolved into the rod photoreceptor at an unknown stage preceding the last common ancestor of extant jawed vertebrates (~420 million years ago Ma). The jawless lampreys provide a unique opportunity to constrain the timing of this advance, as their line diverged ~505 Ma and later displayed high-morphological stability. We recorded with patch electrodes the inner segment photovoltages and with suction electrodes the outer segment photocurrents of Lampetra fluviatilis retinal photoreceptors. Several key functional features of jawed vertebrate rods are present in their phylogenetically homologous photoreceptors in lamprey: crucially, the efficient amplification of the effect of single photons, measured by multiple parameters, and the flow of rod signals into cones. These results make convergent evolution in the jawless and jawed vertebrate lines unlikely and indicate an early origin of rods, implying strong selective pressure toward dim-light vision in Cambrian ecosystems.

/pdf/a-cambrian-origin-for-vertebrate-rods-51x4l5srjj.pdf

A Cambrian origin for vertebrate rods

Mutations in the gene Centrosomal Protein 290 kDa (CEP290) result in multiple ciliopathies ranging from the neonatal lethal disorder Meckel-Gruber Syndrome to multi-systemic disorders such as Joubert Syndrome and Bardet-Biedl Syndrome to nonsyndromic diseases like Leber Congenital Amaurosis (LCA) and retinitis pigmentosa. Results from model organisms and human genetics studies, have suggest that mutations in genes encoding protein components of the transition zone (TZ) and other cilia-associated proteins can function as genetic modifiers and be a source for CEP290 pleiotropy. We investigated the zebrafish cep290fh297/fh297 mutant, which encodes a nonsense mutation (p.Q1217*). This mutant is viable as adults, exhibits scoliosis, and undergoes a slow, progressive cone degeneration. The cep290fh297/fh297 mutants showed partial mislocalization of the transmembrane protein rhodopsin but not of the prenylated proteins rhodopsin kinase (GRK1) or the rod transducin subunit GNB1. Surprisingly, photoreceptor degeneration did not trigger proliferation of Muller glia, but proliferation of rod progenitors in the outer nuclear layer was significantly increased. To determine if heterozygous mutations in other cilia genes could exacerbate retinal degeneration, we bred cep290fh297/fh297 mutants to arl13b, ahi1, and cc2d2a mutant zebrafish lines. While cep290fh297/fh297 mutants lacking a single allele of these genes did not exhibit accelerated photoreceptor degeneration, loss of one alleles of arl13b or ahi1 reduced visual performance in optokinetic response assays at 5 days post fertilization. Our results indicate that the cep290fh297/fh297 mutant is a useful model to study the role of genetic modifiers on photoreceptor degeneration in zebrafish and to explore how progressive photoreceptor degeneration influences regeneration in adult zebrafish.

/pdf/ciliary-genes-arl13b-ahi1-and-cc2d2a-differentially-modify-ynr9kr3r5r.pdf

Ciliary genes arl13b, ahi1 and cc2d2a differentially modify expression of visual acuity phenotypes but do not enhance retinal degeneration due to mutation of cep290 in zebrafish.

Non-technical summary  When rod and cone photoreceptors in the eye respond to light, they need to recover, and the first step in recovery involves a protein called G-protein receptor kinase (GRK). Rods, which underlie night vision, employ a variant called GRK1, whereas cones, which mediate day vision, typically employ a variant called GRK7. We have engineered rod cells in the zebrafish retina that additionally express the cone variant, GRK7. By recording electrically from these modified rods, we have found that they are less sensitive to light than normal rods, in that regard mimicking cones. We have also found evidence to suggest that the size of the cell's response to a single photon (the smallest particle of light) is normal when recovery is mediated by GRK1, but is small (and hence somewhat cone-like) when mediated by GRK7. These results help us understand the differences between rod and cone photoreceptors.

https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/jphysiol.2010.204156

J Sugiyama

Papers

Ectopic expression of cone-specific G-protein-coupled receptor kinase GRK7 in zebrafish rods leads to lower photosensitivity and altered responses