TY - JOUR. T1 - Recoverin. T2 - a Potent Uveitogen for the Induction of Photoreceptor Degeneration in Lewis Rats. AU - Adamus, Grazyna. AU - Ortega, Henry. AU - Witkowska, Danuta. AU - Polans, Arthur. N1 - Copyright: Copyright 2017 Elsevier B.V., All rights reserved.. PY - 1994/10. Y1 - 1994/10. N2 - Recoverin is a calcium-binding protein identified as an autoantigen in a paraneoplastic degenerative disease of the human retina known as cancer-associated retinopathy (CAR). In this study we investigated whether recoverin could elicit an immune response leading to the degeneration of photoreceptor cells in a rodent retina, and whether an animal model of CAR could be developed. Injection of Lewis rats with recoverin caused degeneration of the photoreceptor cells. Several features of uveoretinitis were observed, including vitreous cells, perivasculitis, retinal lesions and complete loss of the photoreceptor cell layer. The first clinical signs of retinal inflammation were observed 10-14 days after ...

Light stimulates rhodopsin in a retinal rod to activate the G protein transducin, which binds to phosphodiesterase (PDE), relieving PDE inhibition and decreasing guanosine 3′,5′-cyclic monophosphate (cGMP) concentration. The decrease in cGMP closes outer segment channels, producing the rod electrical response. Prolonged exposure to light decreases sensitivity and accelerates response kinetics in a process known as light adaptation, mediated at least in part by a decrease in outer segment Ca2+. Recent evidence indicates that one of the mechanisms of adaptation in mammalian rods is down-regulation of PDE. To investigate the effect of light and a possible role of rhodopsin kinase (G protein-coupled receptor kinase 1 [GRK1]) and the GRK1-regulating protein recoverin on PDE modulation, we used transgenic mice with decreased expression of GTPase-accelerating proteins (GAPs) and, consequently, a less rapid decay of the light response. This slowed decay made the effects of genetic manipulation of ...

The retinal response involves recoverin, a neuronal calcium-binding protein which binds onto the photoreceptor cell membrane. Although an approximate binding mechanism has been described, only the latest molecular dynamics simulations made it possible to elucidate in detail its individual stages and unravel the regulatory role of calcium.. Students Štěpán Timr, Roman Pleskot, Jan Kadlec, and others, together with their advisor Pavel Jungwirth shed light on the process in which the binding of two calcium ions to a recoverin molecule promotes the ejection of its hydrophobic myristoyl moiety. This moiety then serves to anchor recoverin to the cell membrane. The specific manner of recoverin binding prevents the action of rhodopsin kinase, the enzyme regulating the rhodopsin cycle. By suppressing the kinase, recoverin makes it ultimately possible for the retina to effectively adapt to changed illumination.. Molecular dynamics simulation has thus proven to be a unique tool to describe the molecular ...

Purpose: : We examined the generation of rod and cone photoreceptors from retinal progenitors in the developing outer nuclear layer (ONL) of the pig retina. Methods: : Retinas were removed from pigs at various development ages, and retinal development was followed by H&E staining of retinal sections. Retinal progenitors and rod and cone photoreceptors progenitors were followed by immunostaining of retina sections. Results: : We identify a population of cone progenitors which are specified and in place in the outer two rows of the developing swine retina before mid-gestation. These cells are marked by Islet1 and recoverin, and they appear before NRL+ rods are specified from PAX6+ retinal progenitor cells. Further, we demonstrate that L/M opsin cones are generated from this population before S opsin cones. Conclusions: : These results provide the first evidence of a distinct population of cone progenitors, which are specified before mid-gestation. These cone progenitors do not differentiate and ...

One of the two photoreceptor cell types of the vertebrate retina. In rods the photopigment is in stacks of membranous disks separate from the outer cell membrane. Rods are more sensitive to light than cones, but rod mediated vision has less spatial and temporal resolution than cone vision ...

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A 47-year-old man noticed quite suddenly visual loss, photopsia and night blindness in August 2003. When he visited our hospital in October 2003, his visual acuity was counting fingers bilaterally, and slit-lamp test revealed normal anterior segments. Funduscopic examination revealed narrowing of the retinal arteries and slight atrophy of retinal pigment epithelium (figure 1A). Goldmann perimetry showed only peripheral islands of vision, and the standard full-field 20 J single flash electroretinogram (ERG) was non-recordable (figure 1B). Chest x-ray, chest CT scanning (figure 1C) and chest MRI (figure 1D) revealed the presence of thymoma, but no other malignancy was found … ...

In the case of antibodies against Hu and Ri all neurone nuclei in the grey matter show a granular fluorescence. Hu antibodies react in the intestine with cell nuclei of the plexus myentericus, whereas Ri antibodies do not. Clinical significance: paraneoplastic neurological syndromes (PNS), indication of a malignoma ...

Cone bipolar cell modifications during retinal degeneration of P23H pigmented L1 rats. Retinal sections stained with antibodies against recoverin in order to vi

To determine whether resveratrol, a natural plant-derived drug, has protective effects against antibody-induced apoptosis of retinal cells in vitro and to provide insights on the mechanism of resveratrol protection. E1A.NR3 retinal cells pretreated with 40 μM resveratrol were grown in the presence of anti-recoverin (Rec-1), anti-enolase (Enol-1) antibodies, and normal purified immunoglobulins. When the cells were exposed to resveratrol before treatment with Enol-1 or Rec-1 antibodies, 30-55% more cells survived compared to the resveratrol-untreated cells. Western blotting showed a reduction in proapoptotic protein Bax in the cytoplasm and mitochondria of resveratrol-treated cells. Resveratrol-pretreated cells also showed a significant decrease in intracellular calcium and an inhibition of caspase-3 activity as compared to the untreated cells. Sirt1 expression was greatly reduced in the cells grown in the presence of Rec-1 and Enol-1, but it increased about five times in the resveratrol-pretreated cells

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the family of voltage-gated potassium (Kv) channel-interacting proteins, which belong to the recoverin branch of the EF-hand superfamily. Members of this family are small calcium binding proteins containing EF-hand-like domains. They are integral subunit components of native Kv4 channel complexes that may regulate A-type currents, and hence neuronal excitability, in response to changes in intracellular calcium. The encoded protein also functions as a calcium-regulated transcriptional repressor, and interacts with presenilins. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008 ...

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1JBA: Three-dimensional structure of guanylyl cyclase activating protein-2, a calcium-sensitive modulator of photoreceptor guanylyl cyclases.

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Purpose: : Peripherin-2 is a tetraspannin transmembrane protein, implicated in retinitis pigmentosa and localized in retinal rod outer segment disk membranes, whose complete 3-dimensional structure is the goal of this nuclear magnetic resonance (NMR) study. Methods: : The 63-residue C-terminal extramembraneous region of peripherin (PERCTER) is crucial to peripherin-mediated fusion.The first target of our structural analysis is the PERCTER, expressed and labeled with 15N, and subjected to structural determination by solution NMR. For this analysis, 3-dimensional HSQC-NOESY and HSQC-TOCSY experiments were utilized, along with 2-dimensional 1H NOESY and TOCSY experiments at various mixing times. This analysis is followed by a similar study of the PERCTER in the presence of a membrane-mimetic, DPC micelles. Results: : The solution structure of the PERCTER that emerges from the NMR data contains considerable alpha-helix at the amino terminus (near the membrane) and is disordered at the C-terminus. In ...

Adds a myristoyl group to the N-terminal glycine residue of certain cellular and viral proteins. Required for normal embryogenesis.

The retina converts light into electrical signals through a series of biochemical steps collectively referred to as phototransduction. Via the optic nerve, thes...

Mouse=100% identity (216/216 amino acids). Target Description: Kv channel-interacting protein 1, Potassium Voltage-Gated Channel Interacting Protein 1 or Kchip1 is a member of the family of voltage-gated potassium (Kv) channel-interacting proteins (KCNIPs), which belongs to the recoverin or neuronal calcium sensor (NCS) family branch of the EF-hand superfamily. Kchip1 associates with Kv4 alpha subunits to form native Kv4 channel complexes. Kchip1 is expressed in the brain and detected in the hippocampus and the dentate gyrus . Diseases associated with KCNIP1 include diastolic hypertension, attention deficit-hyperactivity disorder.. Gene ID: Kcnip1 Kchip1. Antibody Registry ID (RRID): AB_10673162. Physical State: Liquid. ...

Neurocalcin delta (NCALD) is a member of the neuronal calcium sensors protein family. In the retina, NCALD is expressed by ganglion and amacrine cells. NCALD is composed of 4 EF-hand motifs but only 3 of them may bind calcium. The binding of calcium induces a conformational change of the protein which leads to the extrusion of its N-terminal myristoyl group as well as some hydrophilic residues. Th ...

The protein encoded by this gene is a member of neuron-specific calcium-binding proteins family found in the retina and brain. It is highly similar to human hippocalcin protein and nearly identical to the rat and mouse hippocalcin like-1 proteins. It may be involved in the calcium-dependent regulation of rhodopsin phosphorylation and may be of relevance for neuronal signalling in the central nervous system. Several alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Apr 2012 ...

Stimulation of Gi-coupled receptors leads to the activation of mitogen-activated protein kinases (MAP kinases). In several cell types, this appears to be dependent on the activation of p21ras (Ras). Which G-protein subunit(s ...

interface: Tunnel0 Crypto map tag: Tunnel0-head-0, local addr 100.101.102.103 protected vrf: employeeVrf local ident (addr/mask/prot/port): (0.0.0.0/0.0.0.0/0/0) remote ident (addr/mask/prot/port): (0.0.0.0/0.0.0.0/0/0) current_peer 190.191.192.193 port 500 PERMIT, flags={origin_is_acl,} #pkts encaps: 0, #pkts encrypt: 0, #pkts digest: 0 #pkts decaps: 5, #pkts decrypt: 5, #pkts verify: 5 #pkts compressed: 0, #pkts decompressed: 0 #pkts not compressed: 0, #pkts compr. failed: 0 #pkts not decompressed: 0, #pkts decompress failed: 0 #pkts no sa (send) 0, #pkts invalid sa (rcv) 0 #pkts encaps failed (send) 0, #pkts decaps failed (rcv) 0 #pkts invalid prot (recv) 0, #pkts verify failed: 0 #pkts invalid identity (recv) 0, #pkts invalid len (rcv) 0 #pkts replay rollover (send): 0, #pkts replay rollover (rcv) 0 ##pkts replay failed (rcv): 0 #pkts tagged (send): 0, #pkts untagged (rcv): 0 #pkts not tagged (send): 0, #pkts not untagged (rcv): 0 #pkts internal err (send): 0, #pkts internal err (recv) 0 ...

Using synovial sarcoma as a prototype tumor with specific chromosomal translocation and the resultant gene fusion, we generated four synthetic peptides from the SYT-SSX fusion gene according to the HLA-A24 binding motif. We found that one or more of these four peptides reacted in the context of HLA-A24/peptide tetramer with 0.25% or more of circulating CTLps in six (66.7%) of nine synovial sarcoma patients who had either a present or past history of pulmonary metastasis, whereas such high CTLp frequency was detected in none of seven synovial sarcoma patients without metastasis, in 1 of 10 patients with other sarcomas, and in none of the 10 healthy individuals. The specificity of the CTLp to the SYT-SSX sequence was confirmed in three synovial sarcoma patients by using an HLA-A24/Recoverin peptide tetramer. These findings suggest that aberrantly expressed SYT-SSX gene products have primed SYT-SSX-specific CTLps in vivo and increased their frequency in synovial sarcoma patients, especially during ...

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Vision requires the photoreceptors in the eye to rapidly respond to changes in light intensity. These processes are accomplished within rod photoreceptors by the visual pigment rhodopsin that initiates a downstream signaling cascade called phototransduction. Rhodopsin is composed of an apoprotein opsin that is covalently bonded with light sensitive 11-cis retinal. Rhodopsin is activated when 11-cis retinal is photoisomerized into all-trans retinal. This isomerization initiates the phototransduction cascade that culminates in a change in current at the plasma membrane. Rhodopsin, once activated (bleached), can no longer absorb photons to activate phototransduction, and must be regenerated through the visual cycle. To enable the photoreceptors to respond to rapid changes in light intensities, phototransduction must terminate in a timely manner. Deactivation involves phosphorylation of activated rhodopsin by rhodopsin kinase, and then binding of visual arrestin. Exposing rods to daylight bleaches ...

Vision requires the photoreceptors in the eye to rapidly respond to changes in light intensity. These processes are accomplished within rod photoreceptors by the visual pigment rhodopsin that initiates a downstream signaling cascade called phototransduction. Rhodopsin is composed of an apoprotein opsin that is covalently bonded with light sensitive 11-cis retinal. Rhodopsin is activated when 11-cis retinal is photoisomerized into all-trans retinal. This isomerization initiates the phototransduction cascade that culminates in a change in current at the plasma membrane. Rhodopsin, once activated (bleached), can no longer absorb photons to activate phototransduction, and must be regenerated through the visual cycle. To enable the photoreceptors to respond to rapid changes in light intensities, phototransduction must terminate in a timely manner. Deactivation involves phosphorylation of activated rhodopsin by rhodopsin kinase, and then binding of visual arrestin. Exposing rods to daylight bleaches ...

Full Text - Previous studies have shown that PCB1254 has an adverse effect on zebrafish retinal development, but the basic mechanism behind it is not clear. The purpose of this study was to investigate the molecular mechanisms of PCB-induced retinal dysplasia. RT-qPCR, immunoblotting, HE staining and immunofluorescence were adopted to detect the expression at mRNA and protein level. Functional experiments were carried out in 661w cells including CCK-8 assay, caspase-3 assay, and the flow cytometry, while the functional role of miR - 20b was further investigated by using the zebrafish model. The result showed that PCB1254 exposure inhibited cell proliferation and increased the apoptosis of the 661w cells, and the dose–response relationship between the retinal development-related genes (SWS1, CRX, Rho), miR-20b expression and PCB1254 exposure was also discovered. We confirmed that miR-20b targeted FGF2 and GRB2 by constructing a dual luciferase reporter gene and

The pigments in retinal photoreceptor cells absorb varying wavelengths of light, but the central chromophore, the molecule that actually absorbs the photon is identical. Its ability to tune the responsiveness comes from the association with other opsins giving an organism the ability to respond from the near ultraviolet all the way to far red. Interestingly, […]. ...

The pigments in retinal photoreceptor cells absorb varying wavelengths of light, but the central chromophore, the molecule that actually absorbs the photon is identical. Its ability to tune the responsiveness comes from the association with other opsins giving an organism the ability to respond from the near ultraviolet all the way to far red. Interestingly, […]. ...

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These enzymes form some of the cyclic phosphate Ins(cyclic1,2)P(4,5)P2 as well as Ins(1,4,5)P3. They show activity towards phosphatidylinositol, i.e., the activity of EC 4.6.1.13, phosphatidylinositol diacylglycerol-lyase, in vitro at high [Ca2+]. Four beta-isoforms regulated by G-proteins, two gamma-forms regulated by tyrosine kinases, four delta-forms regulated at least in part by calcium and an epsilon-form, probably regulated by the oncogene ras, have been found ...

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Trypanosoma cruzi, a unicellular eukaryotic parasite, is the etiologic agent of Chagas disease, a significant cause of morbidity and mortality in Central and South America (Brener, 1991). Currently, there are 19 countries in which the disease is endemic, with 16 million people infected with T.cruzi and 90 million more at risk (Molyneux, 1997). A 24 kDa flagellar calcium‐binding protein (FCaBP) is found exclusively in the flagellum of the parasite (Engman et al., 1989). FCaBP is a member of the EF‐hand calcium‐binding protein superfamily which possesses four putative binding motifs comprising 75% of the molecule (Engman et al., 1989; Wong et al., 1992; Godsel et al., 1995). FCaBP binds two calcium ions through the third and fourth EF‐hand domains (Maldonado et al., 1999). The calcium‐binding affinities of these sites place FCaBP in the calcium sensor group of EF‐hand proteins, which regulate the activities of other proteins in a calcium‐dependent manner (da Silva and Reinach, ...

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