Turned on by Ca2+! The physiology and pathology of Ca2+-binding proteins in the retina

Polans, Arthur S.; Baehr, Wolfgang; Palczewski, Krzysztof

doi:10.1016/s0166-2236(96)10059-x

Cited by 274 publications

(215 citation statements)

References 79 publications

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“…The phototransduction cascade in light receptors is the first and most striking example of a dynamical gain control. The chemical process is known to involve a complicated cascade of reactions where feedbacks play a large role [26].…”

Section: Feedback Mechanism?mentioning

confidence: 99%

Virtual Retina: A biological retina model and simulator, with contrast gain control

2008

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Section: Feedback Mechanism?mentioning

confidence: 99%

Virtual Retina: A biological retina model and simulator, with contrast gain control

2008

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“…sensation (1). Restoration of the visual chromophore occurs through a complex set of reactions, termed the retinoid cycle, in photoreceptor cells and adjacent retinal pigment epithelial cells (RPE) 1 (2).…”

mentioning

confidence: 99%

“…Restoration of the visual chromophore occurs through a complex set of reactions, termed the retinoid cycle, in photoreceptor cells and adjacent retinal pigment epithelial cells (RPE) 1 (2). Dietary deficiencies in retinoids and retinoid precursors cause visual impairment, developmental abnormalities, and immune deficiency (3,4).…”

mentioning

confidence: 99%

Dual-substrate Specificity Short Chain Retinol Dehydrogenases from the Vertebrate Retina

Haeseleer¹,

Jang²,

Imanishi³

et al. 2002

Journal of Biological Chemistry

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Retinoids are chromophores involved in vision, transcriptional regulation, and cellular differentiation. Members of the short chain alcohol dehydrogenase/reductase superfamily catalyze the transformation of retinol to retinal. Here, we describe the identification and properties of three enzymes from a novel subfamily of four retinol dehydrogenases (RDH11-14) that display dualsubstrate specificity, uniquely metabolizing all-trans-and cis-retinols with C 15 pro-R specificity. RDH11-14 could be involved in the first step of all-trans-and 9-cis-retinoic acid production in many tissues. RDH11-14 fill the gap in our understanding of 11-cis-retinal and all-trans-retinal transformations in photoreceptor (RDH12) and retinal pigment epithelial cells (RDH11). The dualsubstrate specificity of RDH11 explains the minor phenotype associated with mutations in 11-cisretinol dehydrogenase (RDH5) causing fundus albipunctatus in humans and engineered mice lacking RDH5. Furthermore, photoreceptor RDH12 could be involved in the production of 11-cis-retinal from 11-cis-retinol during regeneration of the cone visual pigments. These newly identified enzymes add new elements to important retinoid metabolic pathways that have not been explained by previous genetic and biochemical studies.Retinoids are indispensable light-sensitive elements of vision and also serve as essential modulators of cellular differentiation and proliferation in diverse cell types, including those comprising the epithelium and immune system. Retinoids modulate the growth of both normal and malignant cells through their binding to retinoid receptors. All-trans-retinoic acid signals through specific interactions with the nuclear retinoic acid receptors, whereas its isomer, 9-cis-retinoic acid, is a high affinity ligand of retinoic acid receptors and retinoid X receptors. In the retina, light-dependent photoisomerization of 11-cis-retinylidene to the all-transretinylidene moiety of rod and cone photoreceptors is a key reaction that triggers visual * This research was supported by National Institutes of Health Grants EY08061, CA75173, and DK59125, a grant from Research to Prevent Blindness, Inc. (to the Department of Ophthalmology, University of Washington), and by the E. K. Bishop Foundation. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. S The on-line version of this article (available at http://www.jbc.org) contains Supplemental Figs. 1 and 2 and Tables 1-3. § These authors contributed equally to this work. § § Recipient of a Research to Prevent Blindness Senior Investigator Award. To whom correspondence should be addressed: Dept. of Ophthalmology, University of Washington, Seattle,; E-mail: palczews@u.washington.edu. Transformations of retinoids occur mostly through enzymatic or photochemical reactions, although they readily isomerize non-enzymatically to thermodynamic equilibriu...

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“…Photoreceptor guanylate cyclases (GCs) convert GTP to cGMP, a cyclic nucleotide that serves as internal transmitter of phototransduction in vertebrates (McBee et al 2001;Polans et al 1996). An important feature of photoreceptor GCs is their Ca 2+ sensitivity, which is mediated by Ca 2+ -binding proteins termed GCAPs Sokal et al 2000).…”

Section: Introductionmentioning

confidence: 99%

“…Stimulation of GC at low Ca 2+ constitutes a negative feedback mechanism responsible for return of photoreceptors to the dark state. GCs are integral membrane proteins with one transmembrane domain; GCAPs are soluble CaM-like Ca 2+ -binding proteins (Polans et al 1996).…”

Section: Introductionmentioning

confidence: 99%

Diversity of Guanylate Cyclase-Activating Proteins (GCAPs) in Teleost Fish: Characterization of Three Novel GCAPs (GCAP4, GCAP5, GCAP7) from Zebrafish (Danio rerio) and Prediction of Eight GCAPs (GCAP1-8) in Pufferfish (Fugu rubripes)

et al. 2004

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The guanylate cyclase-activating proteins (GCAPs) are Ca 2+ -binding proteins of the calmodulin (CaM) gene superfamily that function in the regulation of photoreceptor guanylate cyclases (GCs). In the mammalian retina, two GCAPs (GCAP 1-2) and two transmembrane GCs have been identified as part of a complex regulatory system responsive to fluctuating levels of free Ca 2+ . A third GCAP, GCAP3, is expressed in human and zebrafish (Danio rerio) retinas, and a guanylate cyclaseinhibitory protein (GCIP) has been shown to be present in frog cones. To explore the diversity of GCAPs in more detail, we searched the pufferfish (Fugu rubripes) and zebrafish (Danio rerio) genomes for GCAP-related gene sequences (fuGCAPs and zGCAPs, respectively) and found that at least five additional GCAPs (GCAP4-8) are predicted to be present in these species. We identified genomic contigs encoding fuGCAPl-8, fuGCIP, zGCAPl-5, zGCAP7 and zGCIP. We describe cloning, expression and localization of three novel GCAPs present in the zebrafish retina (zGCAP4, zGCAP5, and zGCAP7). The results show that recombinant zGCAP4 stimulated bovine rod outer segment GC in aCa 2+ -dependent manner. RT-PCR with zGCAP specific primers showed specific expression of zGCAPs and zGCIP in the retina, while zGCAPl mRNA is also present in the brain. In situ hybridization with anti-sense zGCAP4, zGCAP5 and zGCAP7 RNA showed exclusive expression in zebrafish cone photoreceptors. The presence of at least eight GCAP genes suggests an unexpected diversity within this subfamily of Ca 2+ -binding proteins in the teleost retina, and suggests additional functions for GCAPs apart from stimulation of GC. Based on genome searches and EST analyses, the mouse and human genomes do not harbor GCAP4-8 or GCIP genes.

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Turned on by Ca2+! The physiology and pathology of Ca2+-binding proteins in the retina

Cited by 274 publications

References 79 publications

Virtual Retina: A biological retina model and simulator, with contrast gain control

Virtual Retina: A biological retina model and simulator, with contrast gain control

Dual-substrate Specificity Short Chain Retinol Dehydrogenases from the Vertebrate Retina

Diversity of Guanylate Cyclase-Activating Proteins (GCAPs) in Teleost Fish: Characterization of Three Novel GCAPs (GCAP4, GCAP5, GCAP7) from Zebrafish (Danio rerio) and Prediction of Eight GCAPs (GCAP1-8) in Pufferfish (Fugu rubripes)

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