Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human, macaque monkey, and rat retinas were immunostained with a polyclonal antibody preparation against purified recoverin, a 23-kD calcium-binding protein isolated from bovine retina that localizes to rods and cones (Dizhoor et al., 1991). In addition to immunoreactive photoreceptors, we have identified subpopulations of recoverin-positive bipolar cells in all three species. Results from immunostaining with progressive dilutions of anti-recoverin and preadsorption of the antibody with a dilution series of purified recoverin showed that photoreceptors and bipolar cells had similar affinities for the antibody and suggested that the molecule recognized by the antibody in both cell types is recoverin. Immunoreactivity for recoverin and protein kinase C, a selective marker for all rod bipolar cells, was found in separate bipolar cell populations. Recoverin immunoreactivity is therefore a characteristic of certain cone bipolar cell types. In rat retina, anti-recoverin labeled two morphologically distinct subpopulations of cone bipolar cells whose axonal arbors stratified at different depths in the inner plexiform layer (IPL). The bipolar cells labeled with anti-recoverin did not correspond to those that were reactive for calbindin, another cone bipolar cell marker. Human and monkey retinas also had two populations of cone bipolar cells that were recoverin-positive. One population showed a distinct pattern of narrow bistratification at the outer border of the IPL and a regular mosaic arrangement of its axonal arbors, suggesting that the entire population of a single cone bipolar type was labeled. Cell density, dendritic morphology, and axonal-field size and stratification indicate that anti-recoverin selectively strains the flat midget (presumed OFF-center) cone bipolar cell type observed previously in Golgi preparations. By contrast the second bipolar cell population had axonal stratification in the inner half of the IPL and showed an unusual but consistent morphology and spatial distribution. Individual cells were intensely stained but were present at an extremely low density (approximately 2-5 cells/mm2). These cells had multibranched dendritic trees characteristic of the diffuse bipolar cell class, but very small axonal fields in the size range of the midget bipolar class. Neither of the two recoverin-positive bipolar cell types in monkey was labeled with anti-calbindin or anti-cholecystokinin. An antibody preparation against bovine pineal hydroxyindole-O-methyltransferase (HIOMT) labeled photoreceptors and bipolar cells that closely resembled the recoverin-positive bipolar cells in human and rat retinas.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Recoverin immunoreactivity in mammalian cone bipolar cells. 842 20

We studied the morphology of bipolar cells in fixed vertical tissue sections of the rat retina by injecting the cells with Lucifer Yellow and neurobiotin. In addition to the rod bipolar cell, nine different putative cone bipolar cell types were distinguished according to the position of their somata in the inner nuclear layer and the branching pattern and stratification level of their axon terminals in the inner plexiform layer. Some of these bipolar cell populations were labeled immunocytochemically in vertical and horizontal sections using antibodies against the calcium-binding protein recoverin, the glutamate transporter GLT-1, the alpha isoform of the protein kinase C, and the Purkinje cell marker L7. These immunocytochemically labeled cell types were characterized in terms of cell density and distribution. We found that rod bipolar cells and GLT-1-positive cone bipolar cells occur at higher densities in a small region located in the upper central retina. This area probably corresponds to the central area, which is the region of highest ganglion cell density. A second peak of rod bipolar cell density in the lower temporal periphery matches the retinal area of binocular overlap. The population densities of the immunocytochemically characterized bipolar cells indicate that at least 50% of all bipolar cells are cone bipolar cells. The variety and total number of cone bipolar cells is surprising because the retina of the rat contains 99% rods. Our findings suggest that cone bipolar cells may play a more important role in the visual system of the rat than previously thought.
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PMID:Immunocytochemical identification of cone bipolar cells in the rat retina. 855 Aug 93

A decrease of cytoplasmic Ca(2+)-concentration in vertebrate photoreceptor cells after illumination is necessary for light adaptation. Although the mechanisms of adaptation is not completely understood, several Ca(2+)-dependent cellular processes have been discovered. Some involve calcium-binding proteins like recoverin, guanylyl cyclase-activating protein and calmodulin, and their target proteins rhodopsin kinase, guanylyl cyclase, the cGMP-gated channel, and NO synthase. The activity of several enzymes or channels is directly controlled by Ca2+ and does not involve calcium-binding proteins. These proteins are pyrophosphatase, protein kinase C and the cGMP-gated channel.
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PMID:Control of photoreceptor proteins by Ca2+. 855 70

We have studied the distribution of the calcium-binding protein calbindin in the adult rabbit retina by using a commercially available antibody and immunocytochemical methods. The most heavily labeled cells are A-type horizontal cells, but B-type horizontal cells are also lightly labeled by this antibody. Among the horizontal cells, there is a mosaic of small, well-labeled somata, which we have identified as a subset of ON cone bipolar cells. In addition, some wide-field amacrine cells and a few large ganglion cells are also labeled for calbindin. The calbindin bipolar cells form a regular mosaic with a peak density of approximately 1,700 cells/mm2, falling to 550 cells/mm2 in the periphery. They account for about one-twelfth of cone bipolar cells, and they are narrowly stratified deep in sublamina 4 of the inner plexiform layer immediately above the rod bipolar terminals. Double-label experiments using an antibody to protein kinase C (PKC) indicate that the calbindin bipolar cells are completely distinct from the population of rod bipolar cells. Rod bipolar cells outnumber the calbindin cone bipolar cells by a factor of four to five. Further double-label experiments show that the calbindin bipolar cells are also labeled for recoverin. The calbindin bipolar cells are well coupled to AII amacrine cells, and they account for roughly 23% of the AII coupled bipolar cells. This suggests that there are three to four additional ON cone bipolar cell types that are coupled to AII amacrine cells. The calbindin cone bipolar cell described in this paper shares many characteristics with a reconstructed cone bipolar cell that forms the most gap junctions with AII amacrine cells (Strettoi et al. [1994] J. Comp. Neurol. 347:139-149). We conclude that these different methodologies provide complementary descriptions of the same cone bipolar cell type. The calbindin antibody defines a subset of cone bipolar cells in the rabbit retina. The cells in this subset are almost certainly the deepest of the cone bipolar cells. The tight stratification of the calbindin cone bipolar cell suggests that the inner plexiform layer is stratified according to depth, with narrow functional divisions within the broad partition of sublamina b, where ON signals are processed. The strength of coupling between the calbindin cone bipolar cells and AII amacrine cells suggests this pathway plays a major role under scotopic conditions.
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PMID:A calbindin-immunoreactive cone bipolar cell type in the rabbit retina. 886 43

We have localized the dopamine D1 receptor in rat retina using a subtype-specific monoclonal antibody. Immunolabelling can be detected in the inner and outer plexiform layers and in a number of cells in the inner nuclear layer. In the inner plexiform layer, labelled processes form four distinct horizontal bands and a series of patches. In order further to characterize the labelling pattern of the D1 receptor antibody, double-labelling experiments were performed with antibodies against population-specific neuronal markers in the retina. Antibodies against tyrosine hydroxylase, choline acetyltransferase, calretinin, calbindin, the glutamate transporter GLT-1, protein kinase C, recoverin and parvalbumin were co-applied with the D1 receptor antibody. With these cell markers we demonstrate that horizontal cells, at least three types of cone bipolar cells and a small number of amacrine cells are immunolabelled for the D1 receptor. In the inner plexiform layer, processes labelled by the D1 receptor antibody are co-stratified with processes labelled by the GLT-1 antibody. D1 receptor-labelled processes are not co-localized with the processes of amacrine cells and ganglion cells labelled by antibodies against tyrosine hydroxylase, choline acetyltransferase or calretinin. Our results indicate that dopamine D1 receptors are localized predominantly to horizontal cells and cone bipolar cells. Furthermore, the spatial disparity between dopaminergic processes and the site of the majority of D1 receptors supports the idea that in the retina dopamine acts as a neuromodulator that diffuses through extracellular space. The localization of D1 receptors to a number of identified cell types enables future physiological work to be directed towards specific synaptic circuits within the retina.
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PMID:Immunohistochemical localization of dopamine D1 receptors in rat retina. 895 93

G protein-coupled receptor kinases (GRKs) constitute a family of six mammalian serine/threonine protein kinases that phosphorylate agonist-bound, or activated, G protein-coupled receptors (GPCRs) as their primary substrates. GRK-mediated receptor phosphorylation rapidly initiates profound impairment of receptor signaling, or desensitization. This review focuses on the regulation of GRK activity by a variety of allosteric and other factors: agonist-stimulated GPCRs, beta gamma subunits of heterotrimeric GTP-binding proteins, phospholipid cofactors, the calcium-binding proteins calmodulin and recoverin, posttranslational isoprenylation and palmitoylation, autophosphorylation, and protein kinase C-mediated GRK phosphorylation. Studies employing recombinant, purified proteins, cell culture, and transgenic animal models attest to the general importance of GRKs in regulating a vast array of GPCRs both in vitro and in vivo.
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PMID:G protein-coupled receptor kinases. 975

Bipolar cells are not only important for visual processing but input from these cells may underlie the reorganization of ganglion cell dendrites in the inner plexiform layer (IPL) during development. Because little is known about the development of bipolar cells, here we have used immunocytochemical markers and dye labeling to identify and follow their differentiation in the neonatal ferret retina. Putative cone bipolar cells were immunoreacted for calbindin and recoverin, and rod bipolar cells were immunostained for protein kinase C (PKC). Our results show that calbindin-immunoreactive cone bipolar cells appear at postnatal day 15 (P15), at which time their axonal terminals are already localized to the inner half of the IPL. By contrast, recoverin-immunoreactive cells with terminals in the IPL are present at birth, but many of these cells may be immature photoreceptors. By the second postnatal week, recoverin-positive cells resembling cone bipolar cells were clearly present, and with increasing age, two distinct strata of immunolabeled processes occupied the IPL. PKC-containing rod bipolar cells emerged by the fourth postnatal week and at this age have stratified arbors in the inner IPL. The early bias of bipolar axonal arbors in terminating in the inner or outer half of the IPL is confirmed by dye labeling of cells with somata in the inner nuclear layer. At P10, several days before ribbon synapses have been previously observed in the ferret IPL, the axon terminals of all dye-labeled bipolar cells were clearly stratified. The results suggest that bipolar cells could provide spatially localized interactions that are suitable for guiding dendritic lamination in the inner retina.
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PMID:Morphological differentiation of bipolar cells in the ferret retina. 1061 93

Ionotropic GABA receptors can mediate presynaptic and postsynaptic inhibition. We assessed the contributions of GABA(A) and GABA(C) receptors to inhibition at the dendrites and axon terminals of ferret retinal bipolar cells by recording currents evoked by focal application of GABA in the retinal slice. Currents elicited at the dendrites were mediated predominantly by GABA(A) receptors, whereas responses evoked at the terminals had GABA(A) and GABA(C) components. The ratio of GABA(C) to GABA(A) (GABA(C):GABA(A)) was highest in rod bipolar cell terminals and variable among cone bipolars, but generally was lower in OFF than in ON classes. Our results also suggest that the GABA(C):GABA(A) could influence the time course of responses. Currents evoked at the terminals decayed slowly in cell types for which the GABA(C):GABA(A) was high, but decayed relatively rapidly in cells for which this ratio was low. Immunohistochemical studies corroborated our physiological results. GABA(A) beta2/3 subunit immunoreactivity was intense in the outer and inner plexiform layers (OPL and IPL, respectively). GABA(C) rho subunit labeling was weak in the OPL but strong in the IPL in which puncta colocalized with terminals of rod bipolars immunoreactive for protein kinase C and of cone bipolars immunoreactive for calbindin or recoverin. These data demonstrate that GABA(A) receptors mediate GABAergic inhibition on bipolar cell dendrites in the OPL, that GABA(A) and GABA(C) receptors mediate inhibition on axon terminals in the IPL, and that the GABA(C):GABA(A) on the terminals may tune the response characteristics of the bipolar cell.
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PMID:Distinct ionotropic GABA receptors mediate presynaptic and postsynaptic inhibition in retinal bipolar cells. 1072 48

Diacylglycerol kinases (DGKs) phosphorylate diacylglycerol produced during stimulus-induced phosphoinositide turnover and attenuate protein kinase C activation. Diacylglycerol kinase alpha is an 82-kDa DGK isoform that is activated in vitro by Ca(2+). The DGK alpha regulatory region includes tandem C1 protein kinase C homology domains and Ca(2+)-binding EF hand motifs. It also contains an N-terminal recoverin homology (RVH) domain that is related to the N termini of the recoverin family of neuronal calcium sensors. To probe the structural basis of Ca(2+) regulation, we expressed a series of DGK alpha deletions spanning its regulatory domain in COS-1 cells. Deletion of the RVH domain resulted in loss of Ca(2+)-dependent activation. Further deletion of the EF hands resulted in a constitutively active enzyme, suggesting that sequences in or near the EF hands are sufficient for autoinhibition. Binding of Ca(2+) to the EF hands protected sites within both the RVH domain and EF hands from trypsin cleavage and increased the phenyl-Sepharose binding of a recombinant DGK alpha fragment that included both the RVH domain and EF hands. These observations suggested that Ca(2+) elicits a concerted conformational change of these two domains. A cationic amphiphile, octadecyltrimethylammonium chloride, also activated DGK alpha. As with Ca(2+), this activation required the RVH domain. However, this agent did not protect the EF hands and RVH domain from trypsin cleavage. These findings indicate that the EF hands and RVH domain act as a functional unit during Ca(2+)-induced DGK alpha activation.
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PMID:A domain with homology to neuronal calcium sensors is required for calcium-dependent activation of diacylglycerol kinase alpha. 1091 59

To identify and characterize the lineage potential of rat neural retina progenitor cells (NRPCs) in vitro and engrafted into rats with retinal degeneration, NRPCs were isolated from neural retinas of embryonic day 17 Long Evans rats and cultured in serum-free or serum-containing media with fibroblast growth factor 2 and neurotrophin 3. After expansion, cellular differentiation was initiated by the withdrawal of these growth factors. Despite forming primary neurospheres, NRPCs cultured in serum-free medium survived poorly after passage. In contrast, NRPCs cultured in serum-containing medium could be expanded for up to 12 passages and differentiated into glial fibrillary acidic protein-positive glial cells and retina-specific neurons expressing rhodopsin, S-antigen, calbindin, recoverin, and calretinin. For in vivo analysis, passage 1 (P1) undifferentiated NRPCs were labeled with bromodeoxyuridine (BrdU), implanted into the subretinal space of Royal College of Surgeons (RCS) rats, and analyzed immunohistochemically 4 weeks postgrafting. The grafted NRPCs showed extensive glial differentiation, irrespective of their topographic localization. A few BrdU-labeled grafted NRPCs expressed protein kinase C, a marker for bipolar and amacrine interneuron-specific differentiation. Other retina-specific or oligodendrocytic differentiation was not detected in the grafted cells. Although NRPCs are capable of self-renewal and multilineage differentiation in vitro, they developed mostly into glial cells following engraftment into the adult retina. These data suggest that the adult retina retains epigenetic signals that are either restrictive for neuronal differentiation or instructive for glial differentiation. Induction of lineage-specific cell differentiation of engrafted NRPCs to facilitate retinal repair will likely require initiation of specific differentiation in vitro prior to grafting and/or modification of the host environment concomitantly with NRPC grafting.
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PMID:Differential lineage restriction of rat retinal progenitor cells in vitro and in vivo. 1221 Aug 40


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