Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Recoverin”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 235 records · Page 13Linked to original sources
PubMed2004

Neuro-ophthalmology and paraneoplastic syndromes.

PURPOSE OF REVIEW: To describe the neuro-ophthalmological manifestations of paraneoplastic syndromes and their immunological associations. RECENT FINDINGS: Neuro-ophthalmological signs and symptoms are usually present in paraneoplastic syndromes of the central nervous system. Unlike opsoclonus, less characteristic eye movement abnormalities are difficult to recognize as presenting symptoms of paraneoplastic syndromes. In this setting, the detection of several antibodies, including anti-Hu, Yo, Ma2, Ri, Tr, CV2/CRMP5 or voltage-gated calcium channel antibodies may help to establish that the neuro-ophthalmological disorder is paraneoplastic. Among the recently characterized antibodies, those against the Ma proteins often associate with brainstem encephalitis and vertical gaze paralysis. A small subset of patients with opsoclonus and ataxia harbor anti-Ri antibodies. In other patients, there is preliminary evidence that the autoantigens of opsoclonus reside in the postsynaptic density, but no dominant antibody marker has been identified. Uveitis and optic neuritis are rare accompaniments of paraneoplastic encephalomyelitis; some of these patients harbor anti-CV2/CRMP5 in association with other antibodies. Studies on paraneoplastic retinopathy indicate that immunity to retinal proteins other than recoverin can result in a similar syndrome to that associated with recoverin antibodies, and that melanoma-associated retinopathy may associate with several retinal antibodies. SUMMARY: There is increasing recognition of an extensive variety of neuro-ophthalmological abnormalities as manifestations of paraneoplastic syndromes and of several antineuronal antibodies as clinical markers of these disorders. Basic immunological studies support the pathogenic role of some of these antibodies, and are elucidating the pathogenic mechanisms that underlie these and other antibody-associated paraneoplastic syndromes.

Autoantibodies↗
PubMed2007

Progenitor cells from the porcine neural retina express photoreceptor markers after transplantation to the subretinal space of allorecipients.

Work in rodents has shown that cultured retinal progenitor cells (RPCs) integrate into the degenerating retina, thus suggesting a potential strategy for treatment of similar degenerative conditions in humans. To demonstrate the relevance of the rodent work to large animals, we derived progenitor cells from the neural retina of the domestic pig and transplanted them to the laser-injured retina of allorecipients. Prior to grafting, immunocytochemical analysis showed that cultured porcine RPCs widely expressed neural cell adhesion molecule, as well as markers consistent with immature neural cells, including nestin, Sox2, and vimentin. Subpopulations expressed the neurodevelopmental markers CD-15, doublecortin, beta-III tubulin, and glial fibrillary acidic protein. Retina-specific markers expressed included the bipolar marker protein kinase Calpha and the photoreceptor-associated markers recoverin and rhodopsin. In addition, reverse transcription-polymerase chain reaction showed expression of the transcription factors Dach1, Hes1, Lhx2, Pax6, Six3, and Six6. Progenitor cells prelabeled with vital dyes survived as allografts in the subretinal space for up to 5 weeks (11 of 12 recipients) without exogenous immune suppression. Grafted cells expressed transducin, recoverin, and rhodopsin in the pig subretinal space, suggestive of differentiation into photoreceptors or, in a few cases, migrated into the neural retina and extended processes, the latter typically showing radial orientation. These results demonstrate that many of the findings seen with rodent RPCs can be duplicated in a large mammal. The pig offers a number of advantages over mice and rats, particularly in terms of functional testing and evaluation of the potential for clinical translation to human subjects. Disclosure of potential conflicts of interest is found at the end of this article.

Animals↗
PubMed2005

Predominant rod photoreceptor degeneration in Leber congenital amaurosis.

PURPOSE: An unusual retinal vascular morphology in an enucleated eye from a patient with Leber congenital amaurosis (LCA) has been associated with a mutation in AIPL1. The AIPL1 protein is expressed in the pineal gland and retinal photoreceptors. In the retina, AIPL1 is expressed in both developing cone and rod photoreceptors, but it is restricted to rod photoreceptors in the adult human retina. Therefore, this study was conducted to determine the photoreceptor phenotype in this LCA patient to determine if photoreceptors were differentially affected. METHODS: Additional genetic screening was performed and the consequences of the H82Y amino acid substitution characterized in an in vitro assay of NUB1 modulation. The morphology of the photoreceptors was examined by light and electron microscopy. Immunohistochemistry and immunofluorescent confocal microscopy was performed using a range of retinal photoreceptor markers. RESULTS: Transfection of the H82Y mutant AIPL1 in SK-N-SH cells revealed a normal subcellular localization and solubility but resulted in an increased ability of AIPL1 to redistribute GFP-NUB1 to the cytoplasm and resolve NUB1 fragment inclusion formation. Morphologically, the LCA retina appeared to be cone-dominant with a single layer of cone-like cells remaining in the central retina. Photoreceptor outer segments were absent and the surviving residual inner segments were severely shortened. Severe degeneration of the LCA retina was associated with upregulation of glial fibrillary acidic protein (GFAP). No signal was detected for AIPL1, rhodopsin, or L/M and S cone opsins in the LCA retina. Double labeling with peanut agglutinin (PNA) and wheat germ agglutinin (WGA) supported a cone-dominant phenotype for the surviving photoreceptors in the LCA retina, as did double labeling for cone arrestin, and rod and cone recoverin. The cone arrestin signal was restricted to the residual photoreceptor inner segments and was not detected in the cell bodies, axons, or axon terminals of the surviving photoreceptors. Recoverin immunoreactivity was most intense in the residual photoreceptor inner segments. CONCLUSIONS: The phenotype in this patient suggests that although AIPL1 is required for the development of normal rod and cone photoreceptor function, it might only be essential for rod and not cone survival in the adult.

Adaptor Proteins, Signal Transducing↗
PubMed1994

Glycinergic synapses in the rod pathway of the rat retina: cone bipolar cells express the alpha 1 subunit of the glycine receptor.

Glycine receptors (GlyRs) and their role in retinal circuitry were analyzed immunocytochemically in the rat retina. Specific antibodies against the alpha 1 subunit of the GlyR and against the GlyR-associated protein gephyrin, respectively, were used. In the inner plexiform layer (IPL), both antibodies produced a punctate label that was shown by electron microscopy to occur at synapses. Gephyrin-like immunoreactivity (-LI) was more widely distributed, indicating that gephyrin might also occur at nonglycinergic synapses. At the ultrastructural level, gephyrin-LI was found at the cytoplasmic face of postsynaptic membranes of amacrine and ganglion cells, but was never detected in bipolar cell axons. Immunoreactivity for the alpha 1 subunit was concentrated in the cleft of conventional synapses made by amacrine cell processes onto ganglion cell dendrites and cone bipolar axons. The latter synapses differ from other glycinergic synapses since they are not labeled by the antibody against gephyrin used in this study. In order to identify the type of bipolar cell involved in these synapses, the distribution of the alpha 1 subunit was compared with that of recoverin-immunoreactive cone bipolar cells and with that of parvalbumin-immunoreactive All-amacrine cells. Double-label immunofluorescence showed that, in the outer part of the IPL, 75% of the alpha 1-immunoreactive puncta were colocalized with recoverin-positive bipolar cell axons and 71% of the alpha 1-immunoreactive puncta were colocalized with parvalbumin-positive All-amacrine processes. Hence, the alpha 1 subunit of the GlyR is present at the chemical synapses established by All-amacrine cells with OFF-cone bipolar cells and OFF-ganglion cells. These synapses play a key role in the transmission of scotopic signals through the OFF-channel of the rod pathway.

Animals↗
PubMed1999

Treatment of paraneoplastic visual loss with intravenous immunoglobulin: report of 3 cases.

BACKGROUND: Paraneoplastic visual loss is an autoimmune disorder believed to be caused by the remote effects of cancer on the retina (cancer-associated retinopathy [CAR]) or optic nerve. Both disorders may result in rapid and complete blindness. Spontaneous recovery of vision has not been reported. The serum of patients with CAR contains autoantibodies against recoverin, enolase, or unidentified retinal proteins. Autopsy examination results of eyes of blind patients with CAR show complete absence of the retinal neurons involved in phototransduction. Corticosteroids and plasmapheresis are the only treatment options previously described. OBJECTIVE: To treat paraneoplastic visual loss. DESIGN AND METHODS: Three patients with metastatic cancer developed rapidly progressive loss of vision. The first patient had visual acuity of hand movements in each eye before intravenous immunoglobulin treatment. The second patient had visual acuity of light perception in both eyes. The third patient's visual acuity was 20/400 OD and 20/20 OS. Diagnostic tests included magnetic resonance imaging of the head and cytologic examination of the cerebrospinal fluid to exclude metastasis as the cause of visual loss and then an electroretinogram and serum tests for autoantibodies against retinal antigens to confirm the clinical diagnosis of CAR. Patients 1 and 2 were treated with intravenous immunoglobulin (400 mg/kg per day) for 5 days; however, patient 3 received only a single dose due to adverse effects consisting of shortness of breath and itching. RESULTS: Within 24 hours of taking the first dose of intravenous immunoglobulin, the visual acuity of patient 1 improved from hand movements only in both eyes to 20/50 OD and 20/200 OS. After the third day of treatment, visual acuity in the left eye further improved to 20/40. Even with the improved acuity, Goldmann visual field perimetry results showed poor responses in both eyes. However, 2 weeks later there was marked visual field improvement, and visual acuity was maintained at 20/50 OD and 20/40 OS. Patient 2 had no improvements and continued to have light perception in both eyes. Patient 3 had improvements in visual field defects but remained 20/400 OD and 20/20 OS. CONCLUSION: Intravenous immunoglobulin may be another treatment option offered to patients with paraneoplastic visual loss in addition to corticosteroids or plasmapheresis because a review of the medical literature has shown no spontaneous improvements of visual function without treatment.

Aged↗
PubMed2001

In vitro inhibition of antirecoverin immunoglobulin-mediated death of mammalian photoreceptor cells.

Cancer-associated retinopathy (CAR) is a blinding disease, which can be mediated by autoimmune reactions with a specific calcium-binding retinal protein, recoverin. A number of recent studies demonstrate that agents that mobilize intracellular calcium can protect neurons from apoptotic death induced by a variety of insults. In this study, we investigated the effect of one such agent, potassium, on the survival of mammalian rod photoreceptors exposed to antirecoverin IgG. Primary cell cultures of rat retinal neurons were grown in a chemically defined medium, and cells were exposed to antirecoverin IgG for 72 hr in various concentrations of potassium and the surviving cells counted. Rod photoreceptors were quantitated using antirhodopsin immunofluorescence microscopy, and total cell numbers were determined by 4',6-diamidino-2-phenylindole (DAPI) staining of nuclei. Apoptosis was evaluated by TdT-mediated biotin-dUTP nick-end labeling (TUNEL), cell death-detection ELISA, and DNA laddering. The present study shows that elevated extracellular K+ ([K+](o)) protects retinal neurons from antirecoverin antibody-mediated cell death. The protective effects of ([K+](o)) were shown to be time- and dose-dependent. The inhibition of antirecoverin IgG-mediated death of photoreceptors by elevated ([K+](o)) suggests that the mobilization of internal calcium stores rescues the cells by interfering with apoptotic signal transduction pathways. These data also suggest that the death of photoreceptor cells occurring in CAR possibly can be prevented by reagents and/or environmental changes that mobilize intracellular calcium.

Animals↗
PubMed1999

Calcium-dependent regulation of rhodopsin phosphorylation.

Depending on ambient light conditions, a rod photoreceptor cell adapts to a light stimulus. For example, when it is kept in the light, its light sensitivity decreases because of light adaptation. The adaptational state is regulated by the Ca2+ concentration in the cytoplasm ([Ca2+]i). The [Ca2+]i is high in the dark and becomes low when the cell is light-adapted. The change in [Ca2+]i is detected by several Ca(2+)-binding proteins that change their conformations by binding Ca2+. S-modulin, found in frog rods, or its bovine homologue recoverin, is a 23 kDa Ca(2+)-binding protein that inhibits rhodopsin phosphorylation at high Ca2+ concentrations by inhibiting rhodopsin kinase. Since rhodopsin phosphorylation is an inactivating mechanism for light-activated rhodopsin (R*), the inhibition of this reaction will prolong the lifetime of R*. In this way, S-modulin is expected to increase the efficiency of phototransduction and therefore the light-sensitivity of rods in the dark. When rods are light-adapted, [Ca2+]i decreases so that the lifetime of the R* is expected to reduce, resulting in a decrease in light sensitivity. Even though it is generally agreed that S-modulin inhibits rhodopsin phosphorylation, its physiological function is not yet well understood.

Adenosine Triphosphate↗
PubMed2003

Goalpha labels ON bipolar cells in the tiger salamander retina.

By using double-label immunocytochemistry and confocal microscopy, we studied rod and cone synaptic contacts, photoreceptor-bipolar cell convergence, and patterns of axon terminal ramification of ON bipolar cells in the tiger salamander retina. An antibody to recoverin, a calcium-binding protein found in photoreceptors and other retinal neurons in various vertebrates, differentially labeled rods and cones by lightly staining rod cell bodies, axons, and synaptic pedicles and heavily staining cone cell bodies and pedicles. An antibody to G(oalpha) labeled most ON bipolar cells, with axon terminals ramified mainly in strata 6-9 and a minor band in stratum 3 of the inner plexiform layer (IPL). Stratum 10 of the IPL was G(oalpha) negative, and previous studies showed that axon terminals of rod-dominated ON bipolar cells are monostratified in that stratum. The axonal morphology of G(oalpha)-positive cells resembled that of the cone-dominated (DBC(C)) or mixed rod and cone ON (DBC(M)) bipolar cells. The G(oalpha)-positive dendritic processes made close contact with all cone pedicles and superficial contact with some rod pedicles, consistent with the idea that G(oalpha) subunits are present in DBC(C)s and DBC(M)s. The size and density of these cells were analyzed, and their spatial distributions were determined. To our knowledge, this is the first study to characterize photoreceptor inputs and axon terminal morphology of a population of ON bipolar cell with the use of a G(oalpha) antibody as an immunomarker in the salamander retina.

Ambystoma↗
PubMed2005

Development of cholinergic amacrine cells is visual activity-dependent in the postnatal mouse retina.

In the present study, we used immunocytochemistry to study the temporal and spatial arrangement of mouse cholinergic amacrine cells during postnatal retinal development under normal light/dark cycles and during visual deprivation. Choline acetyltransferase (ChAT)-immunolabeled cells were detected in the neuroblastic layer (NBL) and in the ganglion cell layer (GCL) at postnatal day 0 (P0). Between P3-5, two characteristic cholinergic bands were clearly identified in the inner plexiform layer (IPL). The signal intensity of somas and processes progressively increased over the first 2 postnatal weeks. Around eye opening at P12, cholinergic neurons were mature-like. This early developmental process was not altered by visual deprivation. After eye opening, the space between the two cholinergic bands increased continuously and the spatial regularity index changed constantly, indicating that the cholinergic neurons possibly underwent refinement during later postnatal development. The changes occurring following eye opening were retarded by visual deprivation. The morphologies of photoreceptors, horizontal cells, recoverin-positive OFF-cone bipolar cells, rod bipolar cells, dopaminergic amacrine cells, and Müller cells appeared normal. Their stratification in the outer plexiform layer (OPL) and the IPL was not affected by visual deprivation. However, glial cells grew vertically across the entire thickness of dark-reared retinas. Our results suggest that the development of cholinergic neurons before eye opening is independent of the lighting conditions. Their development after eye opening is greatly impeded by visual deprivation. This visual activity-dependent phase of development may be a critical period for the maturation and synaptic wiring of cholinergic amacrine cells in the mammalian retina.

Age Factors↗
PubMed2001

Molecular evidence that human ocular ciliary epithelium expresses components involved in phototransduction.

Here we report the expression, in the human ocular ciliary epithelium and in a human nonpigmented (NPE) ciliary epithelial cell line, of genes usually restricted to cone and rod photoreceptor cells of the retina. By RT-PCR and DNA sequencing we identified the expression of rhodopsin and components linked to its deactivation, including rhodopsin kinase, recoverin, and visual arrestin. We also detected the expression of transducin (T-alpha), phosphodiesterase (PDE-alpha), and cGMP-gated channel alpha-subunits. Cultured NPE cells responded to treatment with phorbol ester by enhancing the expression of rhodopsin mRNA three- to fourfold. Indirect immunofluorescence of the intact ciliary epithelium with monoclonal antibodies (MAbs) against rhodopsin, rhodopsin kinase, and visual arrestin revealed labeling preferentially restricted to the NPE cells. Furthermore, Western blot analysis of whole lysates from the pars plicata region of the human ciliary epithelium with MAbs demonstrated immunochemical cross-reactivity with proteins of molecular mass similar to rhodopsin (36 kDa), rhodopsin kinase (64 to 66 kDa), and arrestin (48-52 kDa) from the human retina. These results provide the first molecular evidence that components of a non-visual phototransduction pathway are expressed in the human ocular NPE ciliary epithelium, which may be linked to circadian entrainment tasks.

Animals↗
PubMed2001

Interaction of plant protein Ser/Thr phosphatase PP7 with calmodulin.

We have recently identified PP7, a novel group of plant protein Ser/Thr phosphatases, and hypothesized that PP7 may possess a calmodulin-binding site. To test this hypothesis, we assessed the effect of calmodulin on the activity of recombinant Arabidopsis thaliana PP7 and directly tested interaction between PP7 and calmodulin using surface plasmon resonance. Calmodulin exerted a moderate inhibitory effect on the phosphatase activity of PP7 with submicromolar affinity. PP7 specifically interacted with immobilized calmodulin (but not with recoverin, another EF hand Ca(2+)-binding protein) in a strictly Ca(2+)-dependent manner with nanomolar affinity. Deletion of an insert in the catalytic domain of PP7, predicted to function as a calmodulin-binding site, greatly decreased PP7 binding to calmodulin. These findings provide the first evidence for a plant protein phosphatase directly interacting with calmodulin and indicate that PP7 might be regulated by Ca(2+) levels in vivo.

Arabidopsis↗
PubMed2002

S-modulin.

S-Modulin is a Ca2+-binding protein found in frog rod photoreceptors (1,2) and its bovine homologue is known as recoverin (3,4). In the Ca2+-bound form, S-modulin inhibits rhodopsin phosphorylation5 through inhibition of rhodopsin kinase. (6-9) Because rhodopsin phosphorylation is the quench mechanism of light-activated rhodopsin (R*), (10,11) the inhibition of the phosphorylation by S-modulin probably contributes to increase the lifetime of R* to result in sustained hydrolysis of cGMP5. The Ca2+ concentration decreases in the light in vertebrate photoreceptors, (12-14) and this decrease is essential for light-adaptation. (15,16) Thus, S-modulin is expected to regulate the lifetime of R* and thereby regulate the extent and the time course of hydrolysis of cGMP depending on the intensity of background light. With this mechanism, S-modulin is believed to regulate the waveform of a photoresponse and the efficiency of the light in the generation of a photoresponse.

Animals↗
PubMed1992

Cloning and sequencing of the 23 kDa mouse photoreceptor cell-specific protein.

The 23 kDa protein was localized by immunocytochemistry to photoreceptor cells of the mouse retina, and bovine and mouse cDNA clones were isolated and sequenced. The deduced amino acid sequences showed that the mouse 23 kDa protein is 91% identical to the bovine protein, and is the same as S-modulin, the CAR (cancer-associated retinopathy) protein and recoverin, the Ca(2+)-dependent activator of photoreceptor guanylate cyclase. The amino acid sequence reveals two Ca2+ binding sites, no internal repeats, 59% homology to the chicken visinin protein and 40% homology to calmodulin while Northern analysis demonstrated a single 1.0 kb mRNA species in bovine and mouse retina.

Amino Acid Sequence↗
PubMed1993

The presence of a calcium-sensitive p26-containing complex in bovine retina rod cells.

A protein with apparent M(r) 26 kDa (p26 [(1991) Biokimya 56, 225-228] or recoverin [(1991) Science 251, 915-918]) was suggested to activate GC in a calcium dependent manner in bovine retina rod cells [(1991) Science 251, 915-918; (1991) EMBO J, 10, 793-798]. However, according to our present data homogeneous p26 preparations do not activate the enzyme. At the same time we have revealed a complex of p26 with an unidentified protein, presumably RK, in bovine ROS. Calcium favours formation of the complex whereas EGTA addition (which corresponds to a low free Ca2+ concentration) leads to its dissociation.

Animals↗
PubMed1992

Biochemical mechanism of light adaptation in vertebrate photoreceptors.

Vertebrate photoreceptors can adjust their sensitivity to a wide range of light intensities spanning several orders of magnitude, the phenomenon of which is called light adaptation. Electrophysiological and biochemical studies have revealed that calcium can serve as an intracellular transmitter of light adaptation under the control of cGMP metabolism. After illumination, the cytoplasmic calcium concentration of a photoreceptor decreases, which in turn strongly activates photoreceptor guanylate cyclase. This calcium-dependent effect is mediated by a novel calcium-binding protein (recoverin) and leads to the restoration of the depleted cGMP pool after illumination.

Adaptation, Ocular↗
PubMed2004

Cancer-related diseases of the eye: the role of calcium and calcium-binding proteins.

The eye provides unique opportunities to study complex biochemical pathways and to describe how components of these pathways contribute to the molecular basis of disease. In this article, the role of calcium-binding proteins in cancer-related diseases of the eye is reviewed. First, paraneoplastic syndromes, or so-called remote effects of cancer, arise from damage to tissues distant from any tumor or its metastases. Many of these syndromes are believed to be immune-mediated. Cancer-associated retinopathy (CAR), a blinding disease due to the degeneration of retinal photoreceptor cells, is one of the best characterized of the paraneoplastic syndromes. The CAR autoantigen has been identified as recoverin, a calcium-binding protein of the EF-hand superfamily. Its features as a calcium-binding protein, along with its function in photoreceptor cells and its role as the CAR autoantigen, are discussed. Next, unlike visual symptoms instigated by a distant tumor, ocular melanoma is the primary malignancy originating in the eye. ALG-2 encodes a pro-apoptotic calcium-binding protein that is down-regulated in ocular melanoma, thus providing these tumor cells with a selective advantage. In addition to background discussion of ALG-2, data describing the expression, cellular localization, and dimerization characteristics of ALG-2 in melanoma cells are presented. Biochemical studies of ALG-2 and its interactions with its target Alix/AIP1 also are presented. Finally, the function of ALG-2 in calcium-induced cell death is discussed. Additional calcium-binding proteins in retina and in ocular tumors are described in relation to different disease entities. Such proteins and their expression in the eye provide valuable examples bridging studies of protein chemistry, cellular function, and human disease.

Animals↗
PubMed2005

Characterization of displaced bipolar cells in the tiger salamander retina.

In immunocytochemical studies of the tiger salamander retina, 17% of neurons in the outer nuclear layer did not label for recoverin, a photoreceptor marker. Lucifer yellow injection showed a population of cells in the ONL to be displaced bipolar cells, with axon terminals that stratified exclusively in the OFF sublamina of the inner plexiform layer (IPL), and predominately within the cone-dominated region of the OFF sublamina. Glutamate generated a dendritic cationic conductance increase in all displaced bipolar cells tested, and typical cone-dominated bipolar cell light responses were observed among displaced cells that stratified in the central IPL. We conclude that displaced bipolar cells in the tiger salamander retina are entirely OFF-center cells, and predominately cone-dominated cells.

Animals↗
PubMed2004

Extensive duplications of phototransduction genes in early vertebrate evolution correlate with block (chromosome) duplications.

Many gene families in mammals have members that are expressed more or less uniquely in the retina or differentially in specific retinal cell types. We describe here analyses of nine such gene families with regard to phylogenetic relationships and chromosomal location. The families are opsins, G proteins (alpha, beta, and gamma subunits), phosphodiesterases type 6, cyclic nucleotide-gated channels, G-protein-coupled receptor kinases, arrestins, and recoverins. The results suggest that multiple new gene copies arose in all of these families very early in vertebrate evolution during a period with extensive gene duplications. Many of the new genes arose through duplications of large chromosome regions (blocks of genes) or even entire chromosomes, as shown by linkage with other gene families. Some of the phototransduction families belong to the same duplicated regions and were thus duplicated simultaneously. We conclude that gene duplications in early vertebrate evolution probably helped facilitate the specialization of the retina and the subspecialization of different retinal cell types.

Animals↗