Browse
Submit Data
Databases
API
Help

Dataset Information

12 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Presynaptic localization of GluK5 in rod photoreceptors suggests a novel function of high affinity glutamate receptors in the mammalian retina.

ABSTRACT: Kainate receptors mediate glutamatergic signaling through both pre- and presynaptic receptors. Here, we studied the expression of the high affinity kainate receptor GluK5 in the mouse retina. Double-immunofluoresence labeling and electron microscopic analysis revealed a presynaptic localization of GluK5 in the outer plexiform layer. Unexpectedly, we found GluK5 almost exclusively localized to the presynaptic ribbon of photoreceptor terminals. Moreover, in GluK5-deficient mutant mice the structural integrity of synaptic ribbons was severely altered pointing to a novel function of GluK5 in organizing synaptic ribbons in the presynaptic terminals of rod photoreceptors.

SUBMITTER: Haumann I

PROVIDER: S-EPMC5325551 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Presynaptic localization of GluK5 in rod photoreceptors suggests a novel function of high affinity glutamate receptors in the mammalian retina.

Haumann Iris I Junghans Dirk D Anstötz Max M Frotscher Michael M

PloS one 20170224 2

Kainate receptors mediate glutamatergic signaling through both pre- and presynaptic receptors. Here, we studied the expression of the high affinity kainate receptor GluK5 in the mouse retina. Double-immunofluoresence labeling and electron microscopic analysis revealed a presynaptic localization of GluK5 in the outer plexiform layer. Unexpectedly, we found GluK5 almost exclusively localized to the presynaptic ribbon of photoreceptor terminals. Moreover, in GluK5-deficient mutant mice the structur ...[more]

PMID: 28235022

Similar Datasets

Cone-rod homeobox CRX controls presynaptic active zone formation in photoreceptors of mammalian retina.

Project description:In the mammalian retina, rod and cone photoreceptors transmit the visual information to bipolar neurons through highly specialized ribbon synapses. We have limited understanding of regulatory pathways that guide morphogenesis and organization of photoreceptor presynaptic architecture in the developing retina. While neural retina leucine zipper (NRL) transcription factor determines rod cell fate and function, cone-rod homeobox (CRX) controls the expression of both rod- and cone-specific genes and is critical for terminal differentiation of photoreceptors. A comprehensive immunohistochemical evaluation of Crx-/- (null), CrxRip/+ and CrxRip/Rip (models of dominant congenital blindness) mouse retinas revealed abnormal photoreceptor synapses, with atypical ribbon shape, number and length. Integrated analysis of retinal transcriptomes of Crx-mutants with CRX- and NRL-ChIP-Seq data identified a subset of differentially expressed CRX target genes that encode presynaptic proteins associated with the cytomatrix active zone (CAZ) and synaptic vesicles. Immunohistochemistry of Crx-mutant retina validated aberrant expression of REEP6, PSD95, MPP4, UNC119, UNC13, RGS7 and RGS11, with some reduction in Ribeye and no significant change in immunostaining of RIMS1, RIMS2, Bassoon and Pikachurin. Our studies demonstrate that CRX controls the establishment of CAZ and anchoring of ribbons, but not the formation of ribbon itself, in photoreceptor presynaptic terminals.

| S-EPMC6454433 | biostudies-literature

Transcripts within rod photoreceptors of the Zebrafish retina.

Project description:BACKGROUND:The purpose of this study was to identify transcripts of retinal rod photoreceptors of the zebrafish. The zebrafish is an important animal model for vision science due to rapid and tractable development, persistent neurogenesis of rods throughout the lifespan, and capacity for functional retinal regeneration. RESULTS:Zebrafish rods, and non-rod retinal cells of the xops:eGFP transgenic line, were separated by cell dissociation and fluorescence-activated cell sorting (FACS), followed by RNA-seq. At a false discovery rate of < 0.01, 597 transcripts were upregulated ("enriched") in rods vs. other retinal cells, and 1032 were downregulated ("depleted"). Thirteen thousand three hundred twenty four total transcripts were detected in rods, including many not previously known to be expressed by rods. Forty five transcripts were validated by qPCR in FACS-sorted rods vs. other retinal cells. Transcripts enriched in rods from adult retinas were also enriched in rods from larval and juvenile retinas, and were also enriched in rods sorted from retinas subjected to a neurotoxic lesion and allowed to regenerate. Many transcripts enriched in rods were upregulated in retinas of wildtype retinas vs. those of a zebrafish model for rod degeneration. CONCLUSIONS:We report the generation and validation of an RNA-seq dataset describing the rod transcriptome of the zebrafish, which is now available as a resource for further studies of rod photoreceptor biology and comparative transcriptomics.

| S-EPMC5806438 | biostudies-literature

Frmpd1 Facilitates Trafficking of G-Protein Transducin and Modulates Synaptic Function in Rod Photoreceptors of Mammalian Retina.

Project description:Trafficking of transducin (Gαt) in rod photoreceptors is critical for adaptive and modulatory responses of the retina to varying light intensities. In addition to fine-tuning phototransduction gain in rod outer segments (OSs), light-induced translocation of Gαt to the rod synapse enhances rod to rod bipolar synaptic transmission. Here, we show that the rod-specific loss of Frmpd1 (FERM and PDZ domain containing 1), in the retina of both female and male mice, results in delayed return of Gαt from the synapse back to outer segments in the dark, compromising the capacity of rods to recover from light adaptation. Frmpd1 directly interacts with Gpsm2 (G-protein signaling modulator 2), and the two proteins are required for appropriate sensitization of rod-rod bipolar signaling under saturating light conditions. These studies provide insight into how the trafficking and function of Gαt is modulated to optimize the photoresponse and synaptic transmission of rod photoreceptors in a light-dependent manner.

| S-EPMC9581579 | biostudies-literature

Mature Retina Compensates Functionally for Partial Loss of Rod Photoreceptors.

Project description:Loss of primary neuronal inputs inevitably strikes every neural circuit. The deafferented circuit could propagate, amplify, or mitigate input loss, thus affecting the circuit's output. How the deafferented circuit contributes to the effect on the output is poorly understood because of lack of control over loss of and access to circuit elements. Here, we control the timing and degree of rod photoreceptor ablation in mature mouse retina and uncover compensation. Following loss of half of the rods, rod bipolar cells mitigate the loss by preserving voltage output. Such mitigation allows partial recovery of ganglion cell responses. We conclude that rod death is compensated for in the circuit because ganglion cell responses to stimulation of half of the rods in an unperturbed circuit are weaker than responses after death of half of the rods. The dominant mechanism of such compensation includes homeostatic regulation of inhibition to balance the loss of excitation.

| S-EPMC8049532 | biostudies-literature

Protein kinase CK2 modulates NRL-mediated gene expression in rod photoreceptors of mammalian retina

Project description:Maf-family basic motif leucine zipper protein NRL specifies rod photoreceptor cell fate during retinal development and, in concert with homeodomain protein CRX and other regulatory factors, controls the expression of most rod-expressed genes including the visual pigment gene RHO (rhodopsin). Transcriptional regulatory activity of NRL is modulated by post-translational modifications (PTMs), specially phosphorylation, and mutations in phosphosites can lead to retinal degeneration. During our studies to elucidate NRL-mediated transcriptional regulation, we identified Protein Kinase CK2 in NRL-enriched complexes bound to RHO promoter-enhancer regions and in NRL-enriched high molecular mass fractions from the bovine retina. The presence of CK2 in NRL complexes was confirmed by co-immunoprecipitation from developing and adult mouse retinal extracts. Bioinformatic and mass spectrometry analysis indicated potential phosphorylation of NRL at Ser117 residue by CK2. Co-transfection of Csnk2a1 cDNA encoding CK2 with NRL and CRX reduced the bovine Rho promoter-driven luciferase expression in HEK293 cells, and mutagenesis of NRL-Ser117 residue to Ala restored the reporter gene expression. In concordance, overexpression of CK2 in the mouse retina in vivo by electroporation resulted in reduction of Rho promoter-driven DsRed reporter gene expression. RNA-seq analysis of CK2-electroporated retina revealed altered expression of many transcriptional targets of NRL. Thus, our studies demonstrate an important role of CK2 in context-dependent fine-tuning of NRL function, consequently modulating the expression of rod photoreceptor genes.

2024-04-06 | GSE171665 | GEO

Transcripts within Rod Photoreceptors of the Zebrafish Retina

Project description:Purpose: The purpose of this study was to identify transcripts of rod photoreceptors of the zebrafish, an important animal model for vision science. Methods: Zebrafish rods, and non-rod retinal cells of the XOPS:eGFP transgenic line, were separated by cell dissociation and fluorescence-activated cell sorting (FACS), followed by RNA-seq. Validation studies used qPCR and in situ hybridization. Some transcripts were examined in sorted retinal cell populations of larval and juvenile retinas and regenerated adult retinas, and in a zebrafish model for rod degeneration. Results: At a false discovery rate of <0.01, 597 transcripts were upregulated in rods vs. non-rod retinal cells, and 1032 were downregulated. 13,324 total transcripts were detected in rods, including many not previously known to be expressed by rods. Transcripts enriched in rods from adult retinas were also enriched in rods from larval and juvenile retinas, and were also enriched in regenerated rods. Many transcripts enriched in rods were upregulated in retinas of wildtype retinas vs. those of a zebrafish model for rod degeneration. Conclusions: We report the generation of an RNA-seq dataset describing the rod transcriptome of the zebrafish, which is now available as a resource for further studies of rod photoreceptor biology and comparative transcriptomics.

2018-02-08 | GSE100062 | GEO

Protein kinase CK2 modulates the activity of Maf-family bZIP transcription factor NRL in rod photoreceptors of mammalian retina.

Project description:Maf-family basic motif leucine zipper protein NRL specifies rod photoreceptor cell fate during retinal development and, in concert with homeodomain protein CRX and other regulatory factors, controls the expression of most rod-expressed genes including the visual pigment gene Rhodopsin (Rho). Transcriptional regulatory activity of NRL is modulated by post-translational modifications, especially phosphorylation, and mutations at specific phosphosites can lead to retinal degeneration. During our studies to elucidate NRL-mediated transcriptional regulation, we identified protein kinase CK2 in NRL-enriched complexes bound to Rho promoter-enhancer regions and in NRL-enriched high molecular mass fractions from the bovine retina. The presence of CK2 in NRL complexes was confirmed by co-immunoprecipitation from developing and adult mouse retinal extracts. In vitro kinase assay and bioinformatic analysis indicated phosphorylation of NRL at Ser117 residue by CK2. Co-transfection of Csnk2a1 cDNA encoding murine CK2 with human NRL and CRX reduced the bovine Rho promoter-driven luciferase expression in HEK293 cells and mutagenesis of NRL-Ser117 residue to Ala restored the reporter gene activity. In concordance, overexpression of CK2 in the mouse retina in vivo by electroporation resulted in reduction of Rho promoter-driven DsRed reporter expression as well as the transcript level of many phototransduction genes. Thus, our studies demonstrate that CK2 can phosphorylate Ser117 of NRL. Modulation of NRL activity by CK2 suggests intricate interdependence of transcriptional and signaling pathways in maintaining rod homeostasis.

| S-EPMC9991000 | biostudies-literature

Presynaptic Localization and Possible Function of Calcium-Activated Chloride Channel Anoctamin 1 in the Mammalian Retina.

Project description:Calcium (Ca(2+))-activated chloride (Cl(-)) channels (CaCCs) play a role in the modulation of action potentials and synaptic responses in the somatodendritic regions of central neurons. In the vertebrate retina, large Ca(2+)-activated Cl(-) currents (ICl(Ca)) regulate synaptic transmission at photoreceptor terminals; however, the molecular identity of CaCCs that mediate ICl(Ca) remains unclear. The transmembrane protein, TMEM16A, also called anoctamin 1 (ANO1), has been recently validated as a CaCC and is widely expressed in various secretory epithelia and nervous tissues. Despite the fact that tmem16a was first cloned in the retina, there is little information on its cellular localization and function in the mammalian retina. In this study, we found that ANO1 was abundantly expressed as puncta in 2 synaptic layers. More specifically, ANO1 immunoreactivity was observed in the presynaptic terminals of various retinal neurons, including photoreceptors. ICl(Ca) was first detected in dissociated rod bipolar cells expressing ANO1. ICl(Ca) was abolished by treatment with the Ca(2+) channel blocker Co(2+), the L-type Ca(2+) channel blocker nifedipine, and the Cl(-) channel blockers 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) and niflumic acid (NFA). More specifically, a recently discovered ANO1-selective inhibitor, T16Ainh-A01, and a neutralizing antibody against ANO1 inhibited ICl(Ca) in rod bipolar cells. Under a current-clamping mode, the suppression of ICl(Ca) by using NPPB and T16Ainh-A01 caused a prolonged Ca(2+) spike-like depolarization evoked by current injection in dissociated rod bipolar cells. These results suggest that ANO1 confers ICl(Ca) in retinal neurons and acts as an intrinsic regulator of the presynaptic membrane potential during synaptic transmission.

| S-EPMC3693959 | biostudies-literature

ATP consumption by mammalian rod photoreceptors in darkness and in light.

Project description:Why do vertebrates use rods and cones that hyperpolarize, when in insect eyes a single depolarizing photoreceptor can function at all light levels? We answer this question at least in part with a comprehensive assessment of ATP consumption for mammalian rods from voltages and currents and recently published physiological and biochemical data. In darkness, rods consume 10(8) ATP s(-1), about the same as Drosophila photoreceptors. Ion fluxes associated with phototransduction and synaptic transmission dominate; as in CNS, the contribution of enzymes of the second-messenger cascade is surprisingly small. Suppression of rod responses in daylight closes light-gated channels and reduces total energy consumption by >75%, but in Drosophila light opens channels and increases consumption 5-fold. Rods therefore provide an energy-efficient mechanism not present in rhabdomeric photoreceptors. Rods are metabolically less "costly" than cones, because cones do not saturate in bright light and use more ATP s(-1) for transducin activation and rhodopsin phosphorylation. This helps to explain why the vertebrate retina is duplex, and why some diurnal animals like primates have a small number of cones, concentrated in a region of high acuity.

| S-EPMC2615811 | biostudies-literature

Discs of mammalian rod photoreceptors form through the membrane evagination mechanism.

Project description:Photoreceptor discs are membrane organelles harboring components of the visual signal transduction pathway. The mechanism by which discs form remains enigmatic and is the subject of a major controversy. Classical studies suggest that discs are formed as serial plasma membrane evaginations, whereas a recent alternative postulates that discs, at least in mammalian rods, are formed through intracellular vesicular fusion. We evaluated these models in mouse rods using methods that distinguish between the intracellular vesicular structures and plasma membrane folds independently of their appearance in electron micrographs. The first differentiated membranes exposed to the extracellular space from intracellular membranes; the second interrogated the orientation of protein molecules in new discs. Both approaches revealed that new discs are plasma membrane evaginations. We further demonstrated that vesiculation and plasma membrane enclosure at the site of new disc formation are artifacts of tissue fixation. These data indicate that all vertebrate photoreceptors use the evolutionary conserved membrane evagination mechanism to build their discs.

| S-EPMC4639867 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data