High impact information on GRK7

• In cone-dominant animals as well as in humans, but not in rodents, GRK7, a cone-specific homolog of GRK1, has been identified in cone outer segments [1].
• Knockdown of cone-specific kinase GRK7 in larval zebrafish leads to impaired cone response recovery and delayed dark adaptation [1].
• Highly effective phosphorylation by G protein-coupled receptor kinase 7 of light-activated visual pigment in cones [2].
• Since exposure to light causes a decrease in cAMP levels in rod cells, we propose that phosphorylation of GRK1 and GRK7 by PKA occurs in the dark, when cAMP levels in photoreceptor cells are elevated, and represents a novel mechanism for regulating the activities of these kinases [3].
• Cone deactivation kinetics and GRK1/GRK7 expression in enhanced S cone syndrome caused by mutations in NR2E3 [4].

Biological context of GRK7

• GRK1 and GRK7: unique cellular distribution and widely different activities of opsin phosphorylation in the zebrafish rods and cones [5].
• RESULTS: The human GRK7 gene is located on chromosome 3q21, spans at least 10 Kb and consists of 4 exons [6].
• In the present study, therefore, to identify the GRK1 and GRK7 subtypes expressed in carp photoreceptors, we determined their nucleotide sequences together with their expression patterns in carp retina [7].
• METHODS: Oligonucleotides corresponding to the amino acid sequences conserved in GRK1 or GRK7 were synthesized to screen the GRK subtypes in a carp retinal cDNA library [7].

Anatomical context of GRK7

• GRK7 labeling was absent in all photoreceptors of the ESCS retina [4].
• CONCLUSIONS: The cone-dominant human retina resulting from NR2E3 mutations affords greater understanding of the physiological roles of GRK1 and GRK7 in human cone photoreceptors [4].
• Rod outer segments isolated from bovine retina phosphorylated the FLAG-tagged GRKs in the presence of dibutyryl-cAMP, suggesting that GRK1 and GRK7 are physiologically relevant substrates [3].

Enzymatic interactions of GRK7

• Recombinant human GRK7 catalyzes rhodopsin phosphorylation in a light dependent manner [6].

Other interactions of GRK7

• Immunocytochemistry was performed with antibodies against cone opsins and kinases GRK1 and GRK7 in postmortem normal and ESCS retinal tissue [4].

Analytical, diagnostic and therapeutic context of GRK7

• To understand the molecular basis for these characteristics of cone responses, we focused on the opsin deactivation process initiated by G protein-coupled receptor kinase (GRK) 1 and GRK7 in the zebrafish, an animal model suitable for studies on retinal physiology and biochemistry [5].
• Human and bovine GRK7 cDNAs were isolated by RT-PCR [6].
• Antibodies raised against GRK7 peptides were used to examine the retina specific expression of GRK7 by immunoblotting and its subcellular localization by immunocytochemistry [6].
• Sequence analysis indicates that this protein is orthologous to GRK7 recently cloned from O. latipes, the medaka fish [8].

References