Gene array and expression of mouse retina guanylate cyclase activating proteins 1 and 2

Moran Eye Center, University of Utah Health Science Center, Salt Lake City 84132, USA.
Investigative Ophthalmology &amp Visual Science (Impact Factor: 3.66). 06/1998; 39(6):867-75.
Source: PubMed

ABSTRACT To identify gene arrangement, chromosomal localization, and expression pattern of mouse guanylate cyclase activating proteins GCAP1 and GCAP2, retina-specific Ca2+-binding proteins, and photoreceptor guanylate cyclase activators.
The GCAP1 and GCAP2 genes were cloned from genomic libraries and sequenced. The chromosomal localization of the GCAP array was determined using fluorescent in situ hybridization. The expression of GCAP1 and GCAP2 in mouse retinal tissue was determined by immunocytochemistry.
In this study, the mouse GCAP1 and GCAP2 gene array, its chromosomal localization, RNA transcripts, and immunolocalization of the gene products were fully characterized. The GCAP tail-to-tail array is located at the D band of chromosome 17. Each gene is transcribed into a single transcript of 0.8 kb (GCAP1) and 2 kb (GCAP2). Immunocytochemistry showed that both GCAP genes are expressed in retinal photoreceptor cells, but GCAP2 was nearly undetectable in cones. GCAP2 was also found in amacrine and ganglion cells of the inner retina. Light-adapted and dark-adapted retinas showed no significant difference in the distribution of the most intense GCAP2 staining within the outer segment and outer plexiform layers.
Identical GCAP gene structures and the existence of the tail-to-tail gene array in mouse and human suggest an ancient gene duplication-inversion event preceding mammalian diversification. Identification of both GCAPs in synaptic regions, and of GCAP2 in the inner retina suggest roles of these Ca-binding proteins in addition to regulation of phototransduction.

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Available from: Wolfgang Baehr, Jul 29, 2015
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    • "For comparison, this distance was significantly smaller than the distance between the Cabp5 pattern and the average profile for nine genes expressed in differentiating rod photoreceptor cells (5.05 Ϯ 0.37 normalized tag units; P ϭ 0.0425 by Student's one-tailed t-test), suggesting that at least a subset of bipolar cell-enriched genes have temporal expression patterns that cluster in a distinct window apart from patterns for a subset of rod photoreceptor cell-enriched genes. The late-expressed, previously characterized rod photoreceptor cell-enriched genes included rhodopsin (Rho; Molday and MacKenzie, 1983; Jan and Revel, 1974), guanylate cyclase activator 1a (Guca1a; Subbaraya et al., 1994), aryl hydrocarbon receptor-interacting protein-like 1 (Aipl1; van der Spuy et al., 2002), G protein ␣1 (Gnat1; Lerea et al., 1986), rod outer segment membrane protein 1 (Rom1; Bascom et al., 1992), G protein ␥1 (Gngt1; Peng et al., 1992), guanylate cyclase activator 1b (Guca1b; Howes et al., 1998), G protein-coupled receptor kinase 1 (Grk1; Zhao et al., 1998), and cGMP-specific phosphodiesterase 6G (Pde6g; Tuteja and Farber, 1988). These three additional candidate bipolar cell genes identified from SAGE Fig. 1. "
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    ABSTRACT: Retinal bipolar neurons serve as relay interneurons that connect rod and cone photoreceptor cells to amacrine and ganglion cells. They exhibit diverse morphologies essential for correct routing of photoreceptor cell signals to specific postsynaptic amacrine and ganglion cells. The development and physiology of these interneurons have not been completely defined molecularly. Despite previous identification of genes expressed in several bipolar cell subtypes, molecules that mark each bipolar cell type still await discovery. In this report, novel genetic markers of murine bipolar cells were found. Candidates were initially generated by using microarray analysis of single bipolar cells and mining of retinal serial analysis of gene expression (SAGE) data. These candidates were subsequently tested for expression in bipolar cells by RNA in situ hybridization. Ten new molecular markers were identified, five of which are highly enriched in their expression in bipolar cells within the adult retina. Double-labeling experiments using probes for previously characterized subsets of bipolar cells were performed to identify the subtypes of bipolar cells that express the novel markers. Additionally, the expression of bipolar cell genes was analyzed in Bhlhb4 knockout retinas, in which rod bipolar cells degenerate postnatally, to delineate further the identity of bipolar cells in which novel markers are found. From the analysis of Bhlhb4 mutant retinas, cone bipolar cell gene expression appears to be relatively unaffected by the degeneration of rod bipolar cells. Identification of molecular markers for the various subtypes of bipolar cells will lead to greater insights into the development and function of these diverse interneurons.
    The Journal of Comparative Neurology 04/2008; 507(5):1795-810. DOI:10.1002/cne.21639 · 3.51 Impact Factor
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    • "Acc.: O95843); chimpGCAP3 (Acc.: XP_516639); macGCAP3 (Acc.: XP_001102050); dogGCAP3 (Acc.: XP_545090); cGCAP3 (Acc.: XP_425532); hGCAP3sv (splice variant) (Acc.: AAD19945); macGCAP3 (Acc.: XP_001101961) et al., 1997b; Howes et al., 1998; Cuenca et al., 1998 "
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    ABSTRACT: Detailed biochemical, structural and physiological studies of the role of Ca2(+)-binding proteins in mammalian retinal neurons have yielded new insights into the function of these proteins in normal and pathological states. In phototransduction, a biochemical process that is responsible for the conversion of light into an electrical impulse, guanylate cyclases (GCs) are regulated by GC-activating proteins (GCAPs). These regulatory proteins respond to changes in cytoplasmic Ca2+ concentrations. Disruption of Ca2+ homeostasis in photoreceptor cells by genetic and environmental factors can result ultimately in degeneration of these cells. Pathogenic mutations in GC1 and GCAP1 cause autosomal recessive Leber congenital amaurosis and autosomal dominant cone dystrophy, respectively. This report provides a recent account of the advances, challenges, and possible future prospects of studying this important step in visual transduction that transcends to other neuronal Ca2+ homeostasis processes.
    Sub-cellular biochemistry 02/2007; 45:71-91. DOI:10.1007/978-1-4020-6191-2_4
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    • "For example, one of the GCAP proteins, GCAP-1, is confined to the outer segments, whereas another, GCAP-2, resides predominantly in the inner segment (Dizhoor et al., 1995; Otto-Bruc et al., 1997; Cuenca et al., 1998). Both GCAPs have similar physicochemical properties and confer Ca 2+ sensitivity to guanylate cyclase, and neither undergoes light-dependent translocation (Howes et al., 1998; Strissel et al., 2005). While the reason for their differential localization is entirely unknown, it suggests that, like recoverin , GCAP-2 also has additional signaling functions in the cell. "
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    ABSTRACT: For over 30 years, photoreceptors have been an outstanding model system for elucidating basic principles in sensory transduction and G protein signaling. Recently, photoreceptors have become an equally attractive model for studying many facets of neuronal cell biology. The primary goal of this review is to illustrate this rapidly growing trend. We will highlight the areas of active research in photoreceptor biology that reveal how different specialized compartments of the cell cooperate in fulfilling its overall function: converting photon absorption into changes in neurotransmitter release. The same trend brings us closer to understanding how defects in photoreceptor signaling can lead to cell death and retinal degeneration.
    Neuron 12/2005; 48(3):387-401. DOI:10.1016/j.neuron.2005.10.014 · 15.98 Impact Factor
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