Article

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.

0 Bookmarks
 · 
64 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In vertebrate rods and cones, photon capture by rhodopsin leads to the destruction of cyclic GMP (cGMP) and the subsequent closure of cyclic nucleotide gated ion channels in the outer segment plasma membrane. Replenishment of cGMP and reopening of the channels limit the growth of the photon response and are requisite for its recovery. In different vertebrate retinas, there may be as many as four types of membrane guanylyl cyclases (GCs) for cGMP synthesis. Ten neuronal Ca(2+) sensor proteins could potentially modulate their activities. The mouse is proving to be an effective model for characterizing the roles of individual components because its relative simplicity can be reduced further by genetic engineering. There are two types of GC activating proteins (GCAPs) and two types of GCs in mouse rods, whereas cones express one type of GCAP and one type of GC. Mutant mouse rods and cones bereft of both GCAPs have large, long lasting photon responses. Thus, GCAPs normally mediate negative feedback tied to the light-induced decline in intracellular Ca(2+) that accelerates GC activity to curtail the growth and duration of the photon response. Rods from other mutant mice that express a single GCAP type reveal how the two GCAPs normally work together as a team. Because of its lower Ca(2+) affinity, GCAP1 is the first responder that senses the initial decrease in Ca(2+) following photon absorption and acts to limit response amplitude. GCAP2, with a higher Ca(2+) affinity, is recruited later during the course of the photon response as Ca(2+) levels continue to decline further. The main role of GCAP2 is to provide for a timely response recovery and it is particularly important after exposure to very bright light. The multiplicity of GC isozymes and GCAP homologs in the retinas of other vertebrates confers greater flexibility in shaping the photon responses in order to tune visual sensitivity, dynamic range and frequency response.
    Frontiers in Molecular Neuroscience 06/2014; 7:45.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Summary The complex sensation of vision begins with the relatively simple photoisomerization of the visual pig- ment chromophore 11-cis-retinal to its all-trans config- uration. This event initiates a series of biochemical reactions that are collectively referred to as phototrans- duction, which ultimately lead to a change in the electrochemical signaling of the photoreceptor cell. To operate in a wide range of light intensities, however, the phototransduction pathway must allow for adjustments to background light. These take place through physio- logical adaptation processes that rely primarily on Ca2á ions. While Ca2á may modulate some activities directly, it is more often the case that Ca2á-binding proteins mediate between transient changes in the concentration of Ca2á and the adaptation processes that are asso- ciated with phototransduction. Recently, combined genetic, physiological, and biochemical analyses have yielded new insights about the properties and functions of many phototransduction-specific components, in- cluding some novel Ca2á-binding proteins. Understand- ing these Ca2á-binding proteins will provide a more complete picture of visual transduction, including the mechanisms associated with adaptation, and of related degenerative diseases. BioEssays 22:337-350, 2000. fl 2000 John Wiley & Sons, Inc.
    BioEssays 01/2000; 22(4):337-350. · 4.84 Impact Factor
  • Gastroenterology 01/2011; 140(5). · 12.82 Impact Factor

Full-text (2 Sources)

Download
26 Downloads
Available from
Jun 2, 2014