30 results on '"Zoidl C"'
Search Results
2. Evidence for a role of the N‐terminal domain in subcellular localization of the neuronal connexin36 (Cx36)
- Author
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Zoidl, G., primary, Meier, C., additional, Petrasch‐Parwez, E., additional, Zoidl, C., additional, Habbes, H.‐W., additional, Kremer, M., additional, Srinivas, M., additional, Spray, D.C., additional, and Dermietzel, R., additional
- Published
- 2002
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3. Helix-loop-helix proteins in Schwann cells: A study of regulation and subcellular localization of Ids, REB, and E12/47 during embryonic and postnatal development
- Author
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Stewart, H.J.S, primary, Zoidl, G., additional, Rossner, M., additional, Brennan, A., additional, Zoidl, C., additional, Nave, K.-A., additional, Mirsky, R., additional, and Jessen, K.R., additional
- Published
- 1997
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4. Identification of transcriptionally regulated mRNAs from mouse Schwann cell precursors using modified RNA fingerprinting methods
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Zoidl, G., primary, Blanchard, A.D., additional, Zoidl, C., additional, Dong, Z., additional, Brennan, A., additional, Parmantier, E., additional, Mirsky, R., additional, and Jessen, K.R., additional
- Published
- 1997
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5. P0Is Constitutively Expressed in the Rat Neural Crest and Embryonic Nerves and Is Negatively and Positively Regulated by Axons to Generate Non-Myelin-Forming and Myelin-Forming Schwann Cells, Respectively
- Author
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Lee, M.-J., primary, Brennan, A., additional, Blanchard, A., additional, Zoidl, G., additional, Dong, Z., additional, Tabernero, A., additional, Zoidl, C., additional, Dent, M.A.R., additional, Jessen, K.R., additional, and Mirsky, R., additional
- Published
- 1997
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6. A highly specific and sensitive monoclonal antibody detecting histidine-tagged recombinant proteins
- Author
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Strandmann, E. P. v., primary, Zoidl, C., additional, Nakhei, H., additional, Holewa, B., additional, Strandmann, R. P. v., additional, Lorenz, P., additional, Klein-Hitpass, L., additional, and Ryffel, G. U., additional
- Published
- 1995
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7. Elements and factors involved in tissue-specific and embryonic expression of the liver transcription factor LFB1 in Xenopus laevis
- Author
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Zapp, D, primary, Bartkowski, S, additional, Holewa, B, additional, Zoidl, C, additional, Klein-Hitpass, L, additional, and Ryffel, G U, additional
- Published
- 1993
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8. Developmental regulation and tissue distribution of the liver transcription factor LFB1 (HNF1) in Xenopus laevis.
- Author
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Bartkowski, S, primary, Zapp, D, additional, Weber, H, additional, Eberle, G, additional, Zoidl, C, additional, Senkel, S, additional, Klein-Hitpass, L, additional, and Ryffel, G U, additional
- Published
- 1993
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9. Liver-specific gene expression: A-activator-binding site, a promoter module present in vitellogenin and acute-phase genes
- Author
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Kaling, M, primary, Kugler, W, additional, Ross, K, additional, Zoidl, C, additional, and Ryffel, G U, additional
- Published
- 1991
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10. Genomic structure of the Xenopus laevis liver transcription factor LFB1
- Author
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Zapp, D., Bartkowski, S., Zoidl, C., and Klein-Hitpass, L.
- Published
- 1993
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11. Gap junction Delta-2b ( gjd2b /Cx35.1) depletion causes hyperopia and visual-motor deficiencies in the zebrafish.
- Author
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Brown-Panton CA, Sabour S, Zoidl GSO, Zoidl C, Tabatabaei N, and Zoidl GR
- Abstract
The zebrafish is a powerful model to investigate the developmental roles of electrical synapses because many signaling pathways that regulate the development of the nervous system are highly conserved from fish to humans. Here, we provide evidence linking the mammalian connexin-36 (Cx36) ortholog gjd2b /Cx35.1, a major component of electrical synapses in the zebrafish, with a refractive error in the context of morphological, molecular, and behavioral changes of zebrafish larvae. Two abnormalities were identified. The optical coherence tomography analysis of the adult retina confirmed changes to the refractive properties caused by eye axial length reduction, leading to hyperopic shifts. The gjd2b /Cx35.1 depletion was also correlated with morphological changes to the head and body ratios in larvae. The differential expression of Wnt/ß-catenin signaling genes, connexins, and dopamine receptors suggested a contribution to the observed phenotypic differences. The alteration of visual-motor behavioral responses to abrupt light transitions was aggravated in larvae, providing evidence that cone photoreceptor cell activity was enhanced when gjd2b /Cx35.1 was depleted. The visual disturbances were reversed under low light conditions in gjd2b
-/- /Cx35.1-/- larvae. Since qRT-PCR data demonstrated that two rhodopsin genes were downregulated, we speculated that rod photoreceptor cells in gjd2b /Cx35.1-/- larvae were less sensitive to bright light transitions, thus providing additional evidence that a cone-mediated process caused the VMR light-ON hyperactivity after losing Cx35.1 expression. Together, this study provides evidence for the role of gjd2b /Cx35.1 in the development of the visual system and visually guided behaviors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Brown-Panton, Sabour, Zoidl, Zoidl, Tabatabaei and Zoidl.)- Published
- 2023
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12. Panx1 channels promote both anti- and pro-seizure-like activities in the zebrafish via p2rx7 receptors and ATP signaling.
- Author
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Whyte-Fagundes P, Taskina D, Safarian N, Zoidl C, Carlen PL, Donaldson LW, and Zoidl GR
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- Adenosine Triphosphate metabolism, Animals, Nerve Tissue Proteins metabolism, Seizures genetics, Seizures metabolism, Signal Transduction, Zebrafish, Connexins metabolism, Receptors, Purinergic P2X7 metabolism, Xenopus Proteins metabolism
- Abstract
The molecular mechanisms of excitation/inhibition imbalances promoting seizure generation in epilepsy patients are not fully understood. Evidence suggests that Pannexin1 (Panx1), an ATP release channel, modulates the excitability of the brain. In this report, we performed electrophysiological, behavioral, and molecular phenotyping experiments on zebrafish larvae bearing genetic or pharmacological knockouts of Panx1a and Panx1b channels, each homologous to human PANX1. When Panx1a function is lost, or both channels are under pharmacological blockade, seizures with ictal-like events and seizure-like locomotion are reduced in the presence of pentylenetetrazol. Transcriptome profiling by RNA-seq demonstrates a spectrum of distinct metabolic and cell signaling states which correlate with the loss of Panx1a. Furthermore, the pro- and anticonvulsant activities of both Panx1 channels affect ATP release and involve the purinergic receptor P2rx7. Our findings suggest a subfunctionalization of Panx1 enabling dual roles in seizures, providing a unique and comprehensive perspective to understanding seizure mechanisms in the context of this channel., (© 2022. The Author(s).)
- Published
- 2022
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13. Panx1b Modulates the Luminance Response and Direction of Locomotion in the Zebrafish.
- Author
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Safarian N, Houshangi-Tabrizi S, Zoidl C, and Zoidl GR
- Subjects
- Animals, Connexins genetics, RNA-Seq, Zebrafish genetics, Zebrafish Proteins genetics, Connexins metabolism, Motion Perception, Swimming, Vision, Ocular, Zebrafish metabolism, Zebrafish Proteins metabolism
- Abstract
Pannexin1 (Panx1) can form ATP-permeable channels that play roles in the physiology of the visual system. In the zebrafish two ohnologs of Panx1, Panx1a and Panx1b, have unique and shared channel properties and tissue expression patterns. Panx1a channels are located in horizontal cells of the outer retina and modulate light decrement detection through an ATP/pH-dependent mechanisms and adenosine/dopamine signaling. Here, we decipher how the strategic localization of Panx1b channels in the inner retina and ganglion cell layer modulates visually evoked motor behavior. We describe a panx1b knockout model generated by TALEN technology. The RNA-seq analysis of 6 days post-fertilization larvae is confirmed by real-time PCR and paired with testing of locomotion behaviors by visual motor and optomotor response tests. We show that the loss of Panx1b channels disrupts the retinal response to an abrupt loss of illumination and it decreases the larval ability to follow leftward direction of locomotion in low light conditions. We concluded that the loss of Panx1b channels compromises the final output of luminance as well as motion detection. The Panx1b protein also emerges as a modulator of the circadian clock system. The disruption of the circadian clock system in mutants suggests that Panx1b could participate in non-image forming processes in the inner retina.
- Published
- 2021
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14. Convergent NMDA receptor-Pannexin1 signaling pathways regulate the interaction of CaMKII with Connexin-36.
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Siu RCF, Kotova A, Timonina K, Zoidl C, and Zoidl GR
- Subjects
- Animals, Calcium metabolism, Calcium Signaling, Cell Line, Gap Junctions metabolism, Mice, Neurons metabolism, Protein Interaction Maps, Gap Junction delta-2 Protein, Calcium-Calmodulin-Dependent Protein Kinase Type 2 metabolism, Connexins metabolism, Nerve Tissue Proteins metabolism, Receptors, N-Methyl-D-Aspartate metabolism, Signal Transduction
- Abstract
Ca
2+ /calmodulin-dependent protein kinase II (CaMKII) binding and phosphorylation of mammalian connexin-36 (Cx36) potentiate electrical coupling. To explain the molecular mechanism of how Cx36 modifies plasticity at gap junctions, we investigated the roles of ionotropic N-methyl-D-aspartate receptors and pannexin1 (Panx1) channels in regulating Cx36 binding to CaMKII. Pharmacological interference and site-directed mutagenesis of protein interaction sites shows that NMDA receptor activation opens Cx36 channels, causing the Cx36- CaMKII binding complex to adopt a compact conformation. Ectopic Panx1 expression in a Panx1 knock-down cell line is required to restore CaMKII mediated opening of Cx36. Furthermore, blocking of Src-family kinase activation of Panx1 is sufficient to prevent the opening of Cx36 channels. Our research demonstrates that the efficacy of Cx36 channels requires convergent calcium-dependent signaling processes in which activation of ionotropic N-methyl-D-aspartate receptor, Src-family kinase, and Pannexin1 open Cx36. Our results add to the best of our knowledge a new twist to mounting evidence for molecular communication between these core components of electrical and chemical synapses.- Published
- 2021
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15. Visuomotor deficiency in panx1a knockout zebrafish is linked to dopaminergic signaling.
- Author
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Safarian N, Whyte-Fagundes P, Zoidl C, Grigull J, and Zoidl G
- Subjects
- Animals, Dopamine D2 Receptor Antagonists pharmacology, Haloperidol pharmacology, Larva drug effects, Larva metabolism, Neurons drug effects, Receptors, Dopamine D2 metabolism, Retina drug effects, Retina metabolism, Signal Transduction drug effects, Superior Colliculi drug effects, Superior Colliculi metabolism, Swimming physiology, Vision, Ocular drug effects, Connexins metabolism, Dopamine metabolism, Neurons metabolism, Signal Transduction physiology, Vision, Ocular physiology, Zebrafish metabolism, Zebrafish Proteins metabolism
- Abstract
Pannexin 1 (Panx1) forms ATP-permeable membrane channels that play roles in the nervous system. The analysis of roles in both standard and pathological conditions benefits from a model organism with rapid development and early onset of behaviors. Such a model was developed by ablating the zebrafish panx1a gene using TALEN technology. Here, RNA-seq analysis of 6 days post fertilization larvae were confirmed by Real-Time PCR and paired with testing visual-motor behavior and in vivo electrophysiology. Results demonstrated that loss of panx1a specifically affected the expression of gene classes representing the development of the visual system and visual processing. Abnormal swimming behavior in the dark and the expression regulation of pre-and postsynaptic biomarkers suggested changes in dopaminergic signaling. Indeed, altered visuomotor behavior in the absence of functional Panx1a was evoked through D1/D2-like receptor agonist treatment and rescued with the D2-like receptor antagonist Haloperidol. Local field potentials recorded from superficial areas of the optic tectum receiving input from the retina confirmed abnormal responses to visual stimuli, which resembled treatments with a dopamine receptor agonist or pharmacological blocking of Panx1a. We conclude that Panx1a functions are relevant at a time point when neuronal networks supporting visual-motor functions undergo modifications preparing for complex behaviors of freely swimming fish.
- Published
- 2020
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16. Tubulin-Dependent Transport of Connexin-36 Potentiates the Size and Strength of Electrical Synapses.
- Author
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Brown CA, Del Corsso C, Zoidl C, Donaldson LW, Spray DC, and Zoidl G
- Subjects
- Animals, Biomechanical Phenomena, Connexins genetics, Electrical Synapses genetics, Gap Junctions genetics, Mice, Neuronal Plasticity physiology, Protein Binding, Protein Transport, Rats, Tumor Cells, Cultured, Gap Junction delta-2 Protein, Connexins metabolism, Electrical Synapses physiology, Gap Junctions metabolism, Neurons physiology, Tubulin physiology
- Abstract
Connexin-36 (Cx36) electrical synapses strengthen transmission in a calcium/calmodulin (CaM)/calmodulin-dependent kinase II (CaMKII)-dependent manner similar to a mechanism whereby the N-methyl-D-aspartate (NMDA) receptor subunit NR2B facilitates chemical transmission. Since NR2B-microtubule interactions recruit receptors to the cell membrane during plasticity, we hypothesized an analogous modality for Cx36. We determined that Cx36 binding to tubulin at the carboxy-terminal domain was distinct from Cx43 and NR2B by binding a motif overlapping with the CaM and CaMKII binding motifs. Dual patch-clamp recordings demonstrated that pharmacological interference of the cytoskeleton and deleting the binding motif at the Cx36 carboxyl-terminal (CT) reversibly abolished Cx36 plasticity. Mechanistic details of trafficking to the gap-junction plaque (GJP) were probed pharmacologically and through mutational analysis, all of which affected GJP size and formation between cell pairs. Lys279, Ile280, and Lys281 positions were particularly critical. This study demonstrates that tubulin-dependent transport of Cx36 potentiates synaptic strength by delivering channels to GJPs, reinforcing the role of protein transport at chemical and electrical synapses to fine-tune communication between neurons., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.
- Published
- 2019
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17. A Potential Compensatory Role of Panx3 in the VNO of a Panx1 Knock Out Mouse Model.
- Author
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Whyte-Fagundes P, Kurtenbach S, Zoidl C, Shestopalov VI, Carlen PL, and Zoidl G
- Abstract
Pannexins (Panx) are integral membrane proteins, with Panx1 being the best-characterized member of the protein family. Panx1 is implicated in sensory processing, and knockout (KO) animal models have become the primary tool to investigate the role(s) of Panx1 in sensory systems. Extending previous work from our group on primary olfaction, the expression patterns of Panxs in the vomeronasal organ (VNO), an auxiliary olfactory sense organ with a role in reproduction and social behavior, were compared. Using qRT-PCR and Immunohistochemistry (IHC), we confirmed the loss of Panx1, found similar Panx2 expression levels in both models, and a significant upregulation of Panx3 in mice with a global ablation of Panx1. Specifically, Panx3 showed upregulated expression in nerve fibers of the non-sensory epithelial layer in juvenile and adult KO mice and in the sensory layer of adults, which overlaps with Panx1 expression areas in WT populations. Since both social behavior and evoked ATP release in the VNO was not compromised in KO animals, we hypothesized that Panx3 could compensate for the loss of Panx1. This led us to compare Panx1 and Panx3 channels in vitro , demonstrating similar dye uptake and ATP release properties. Outcomes of this study strongly suggest that Panx3 may functionally compensate for the loss of Panx1 in the VNO of the olfactory system, ensuring sustained chemosensory processing. This finding extends previous reports on the upregulation of Panx3 in arterial walls and the skin of Panx1 KO mice, suggesting that roles of Panx1 warrant uncharacterized safeguarding mechanisms involving Panx3.
- Published
- 2018
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18. Structural and Functional Consequences of Connexin 36 (Cx36) Interaction with Calmodulin.
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Siu RC, Smirnova E, Brown CA, Zoidl C, Spray DC, Donaldson LW, and Zoidl G
- Abstract
Functional plasticity of neuronal gap junctions involves the interaction of the neuronal connexin36 with calcium/calmodulin-dependent kinase II (CaMKII). The important relationship between Cx36 and CaMKII must also be considered in the context of another protein partner, Ca
2+ loaded calmodulin, binding an overlapping site in the carboxy-terminus of Cx36. We demonstrate that CaM and CaMKII binding to Cx36 is calcium-dependent, with Cx36 able to engage with CaM outside of the gap junction plaque. Furthermore, Ca2+ loaded calmodulin activates Cx36 channels, which is different to other connexins. The NMR solution structure demonstrates that CaM binds Cx36 in its characteristic compact state with major hydrophobic contributions arising from W277 at anchor position 1 and V284 at position 8 of Cx36. Our results establish Cx36 as a hub binding Ca2+ loaded CaM and they identify this interaction as a critical step with implications for functions preceding the initiation of CaMKII mediated plasticity at electrical synapses.- Published
- 2016
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19. Differential expression of astrocytic connexins in a mouse model of prenatal alcohol exposure.
- Author
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Ramani M, Mylvaganam S, Krawczyk M, Wang L, Zoidl C, Brien J, Reynolds JN, Kapur B, Poulter MO, Zoidl G, and Carlen PL
- Subjects
- Animals, Astrocytes metabolism, Cerebral Cortex drug effects, Cerebral Cortex metabolism, Connexin 30 genetics, Connexin 30 metabolism, Connexin 43 genetics, Disease Models, Animal, Female, Gap Junctions drug effects, Gap Junctions metabolism, Hippocampus drug effects, Hippocampus metabolism, Male, Mice, Inbred C57BL, Neurons drug effects, Neurons metabolism, Pregnancy, Alcohols pharmacology, Astrocytes drug effects, Connexin 43 metabolism, Prenatal Exposure Delayed Effects metabolism
- Abstract
Maternal alcohol consumption during gestation can cause serious injury to the fetus, and may result in a range of physiological and behavioral impairments, including increased seizure susceptibility, that are collectively termed fetal alcohol spectrum disorder (FASD). The cellular mechanisms underlying increased seizure susceptibility in FASD are not well understood, but could involve altered excitatory coupling of neuronal populations mediated by gap junction proteins. We utilized a mouse model of the prenatal alcohol exposure (PAE) to study the expression pattern of connexin (Cx) major components of gap junctions, and pannexin proteins, which form membrane channels, in the brain of 2-3weeks old PAE and control postnatal offspring. PAE during the first trimester-equivalent period of pregnancy in mice resulted in significant up-regulation of Cx30 mRNA and Cx30 total protein in the hippocampus of PAE animals compared to age-matched controls. Surface level expression of both dimeric and monomeric Cx30 were also found to be significantly up-regulated in both hippocampus and cerebral cortex of PAE animals compared to age-matched controls. On the membrane surface, the fast migrating form of Cx43 was found to be up-regulated in the hippocampus of PAE mice. However, we did not see any up-regulation of the phosphorylated forms of Cx43 on the membrane surface. These results indicate that the expression and processing of astrocytic connexins (Cx30, Cx43) are up-regulated in the brain of PAE offspring, and these changes could play a role in the cerebral hyperexcitability observed in these animals., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2016
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20. Investigation of olfactory function in a Panx1 knock out mouse model.
- Author
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Kurtenbach S, Whyte-Fagundes P, Gelis L, Kurtenbach S, Brazil E, Zoidl C, Hatt H, Shestopalov VI, and Zoidl G
- Abstract
Pannexin 1 (Panx1), the most extensively investigated member of a channel-forming protein family, is able to form pores conducting molecules up to 1.5 kDa, like ATP, upon activation. In the olfactory epithelium (OE), ATP modulates olfactory responsiveness and plays a role in proliferation and differentiation of olfactory sensory neurons (OSNs). This process continuously takes place in the OE, as neurons are replaced throughout the whole lifespan. The recent discovery of Panx1 expression in the OE raises the question whether Panx1 mediates ATP release responsible for modulating chemosensory function. In this study, we analyzed pannexin expression in the OE and a possible role of Panx1 in olfactory function using a Panx1(-/-) mouse line with a global ablation of Panx1. This mouse model has been previously used to investigate Panx1 functions in the retina and adult hippocampus. Here, qPCR, in-situ hybridization, and immunohistochemistry (IHC) demonstrated that Panx1 is expressed in axon bundles deriving from sensory neurons of the OE. The localization, distribution, and expression of major olfactory signal transduction proteins were not significantly altered in Panx1(-/-) mice. Further, functional analysis of Panx1(-/-) animals does not reveal any major impairment in odor perception, indicated by electroolfactogram (EOG) measurements and behavioral testing. However, ATP release evoked by potassium gluconate application was reduced in Panx1(-/-) mice. This result is consistent with previous reports on ATP release in isolated erythrocytes and spinal or lumbar cord preparations from Panx1(-/-) mice, suggesting that Panx1 is one of several alternative pathways to release ATP in the olfactory system.
- Published
- 2014
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21. Pannexin1 channel proteins in the zebrafish retina have shared and unique properties.
- Author
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Kurtenbach S, Prochnow N, Kurtenbach S, Klooster J, Zoidl C, Dermietzel R, Kamermans M, and Zoidl G
- Subjects
- Animals, Base Sequence, Blotting, Western, Connexins metabolism, Immunohistochemistry, Kinetics, Microscopy, Confocal, Molecular Sequence Data, Mutagenesis, Site-Directed, Oligonucleotides genetics, Patch-Clamp Techniques, Protein Isoforms genetics, Protein Isoforms metabolism, Real-Time Polymerase Chain Reaction, Sequence Analysis, DNA, Species Specificity, Zebrafish metabolism, Zebrafish Proteins metabolism, Connexins genetics, Evolution, Molecular, Gene Expression Regulation genetics, Phylogeny, Retina metabolism, Zebrafish genetics, Zebrafish Proteins genetics
- Abstract
In mammals, a single pannexin1 gene (Panx1) is widely expressed in the CNS including the inner and outer retinae, forming large-pore voltage-gated membrane channels, which are involved in calcium and ATP signaling. Previously, we discovered that zebrafish lack Panx1 expression in the inner retina, with drPanx1a exclusively expressed in horizontal cells of the outer retina. Here, we characterize a second drPanx1 protein, drPanx1b, generated by whole-genome duplications during teleost evolution. Homology searches strongly support the presence of pannexin sequences in cartilaginous fish and provide evidence that pannexins evolved when urochordata and chordata evolution split. Further, we confirm Panx1 ohnologs being solely present in teleosts. A hallmark of differential expression of drPanx1a and drPanx1b in various zebrafish brain areas is the non-overlapping protein localization of drPanx1a in the outer and drPanx1b in the inner fish retina. A functional comparison of the evolutionary distant fish and mouse Panx1s revealed both, preserved and unique properties. Preserved functions are the capability to form channels opening at resting potential, which are sensitive to known gap junction and hemichannel blockers, intracellular calcium, extracellular ATP and pH changes. However, drPanx1b is unique due to its highly complex glycosylation pattern and distinct electrophysiological gating kinetics. The existence of two Panx1 proteins in zebrafish displaying distinct tissue distribution, protein modification and electrophysiological properties, suggests that both proteins fulfill different functions in vivo.
- Published
- 2013
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22. Molecular diversity of connexin and pannexin genes in the retina of the zebrafish Danio rerio.
- Author
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Zoidl G, Kremer M, Zoidl C, Bunse S, and Dermietzel R
- Subjects
- Amino Acid Sequence, Animals, Cloning, Molecular, Connexins metabolism, Conserved Sequence, Gap Junctions metabolism, Humans, Molecular Sequence Data, Protein Isoforms genetics, Protein Isoforms metabolism, Zebrafish metabolism, Connexins genetics, Genetic Variation, Retina metabolism, Zebrafish genetics
- Abstract
Gap junctions are among the most widely distributed cell structures involved in cell-to-cell communication. Recently completed genome sequencing projects including species from all major phyla have demonstrated the existence of three distinct gene families, the connexins, pannexins, and innexins, as molecular building blocks of gap junctional communication. In the present study, the authors have addressed the molecular complexity of gap junction gene expression in the zebrafish retina, a remarkably complex sensory organ built by diverse neuronal subtypes. Using a combination of cDNA library and genomic DNA library screening and/or RACE technology, the authors have cloned, in addition to the four previously reported connexins, seven novel connexins and four pannexin transcripts resembling two pannexin genes. This result demonstrates the presence of two distinct gap junction type gene families and indicates a remarkable molecular and functional diversity of gap junction-mediated coupling in the fish retina.
- Published
- 2008
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23. Identification and characterization of ZFP-57, a novel zinc finger transcription factor in the mammalian peripheral nervous system.
- Author
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Alonso MB, Zoidl G, Taveggia C, Bosse F, Zoidl C, Rahman M, Parmantier E, Dean CH, Harris BS, Wrabetz L, Müller HW, Jessen KR, and Mirsky R
- Subjects
- Amino Acid Sequence, Animals, Cell Division, Cell Lineage, DNA-Binding Proteins genetics, DNA-Binding Proteins physiology, Embryonic and Fetal Development, Fibroblast Growth Factor 2 pharmacology, Interleukin-6 pharmacology, Leukemia Inhibitory Factor, Mice, Molecular Sequence Data, Nuclear Proteins genetics, Nuclear Proteins physiology, Promoter Regions, Genetic, RNA, Messenger analysis, Rats, Repressor Proteins physiology, Swiss 3T3 Cells, DNA-Binding Proteins analysis, Nuclear Proteins analysis, Schwann Cells chemistry, Sciatic Nerve chemistry, Zinc Fingers
- Abstract
To isolate new zinc finger genes expressed at early stages of peripheral nerve development, we have used PCR to amplify conserved zinc finger sequences. RNA from rat embryonic day 12 and 13 sciatic nerves, a stage when nerves contain Schwann cell precursors, was used to identify several genes not previously described in Schwann cells. One of them, zinc finger protein (ZFP)-57, proved to be the homologue of a mouse gene found in F9 teratocarcinoma cells. Its mRNA expression profile within embryonic and adult normal and transected peripheral nerves, and its distribution in the rest of the nervous system is described. High levels of expression are seen in embryonic nerves and spinal cord. These drop rapidly during the first few weeks after birth, a pattern mirrored in other parts of the nervous system. ZFP-57 localizes to the nucleus of Schwann and other cells. The sequence contains an N-terminal Krüppel-associated box (KRAB) domain and ZFP-57 constructs containing green fluorescent protein reveal that the protein colocalizes with heterochromatin protein 1alpha to centromeric heterochromatin in a characteristic speckled pattern in NIH3T3 cells. The KRAB domain is required for this localization, because constructs lacking it target the protein to the nucleus but not to the centromeric heterochromatin. When fused to a heterologous DNA binding domain, the KRAB domain of ZFP-57 represses transcription, and full-length ZFP-57 represses Schwann cell transcription from myelin basic protein and P(0) promoters in co-transfection assays. Zfp-57 mRNA is up-regulated in Schwann cells in response to leukemia inhibitory factor and fibroblast growth factor 2.
- Published
- 2004
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24. Molecular cloning and functional expression of zfCx52.6: a novel connexin with hemichannel-forming properties expressed in horizontal cells of the zebrafish retina.
- Author
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Zoidl G, Bruzzone R, Weickert S, Kremer M, Zoidl C, Mitropoulou G, Srinivas M, Spray DC, and Dermietzel R
- Subjects
- Amino Acid Sequence, Animals, Cloning, Molecular, Connexins metabolism, Gap Junctions metabolism, Humans, Molecular Sequence Data, Sequence Alignment, Xenopus, Zebrafish Proteins metabolism, Connexins genetics, Retina metabolism, Zebrafish metabolism, Zebrafish Proteins genetics
- Abstract
Gap junction-mediated electrical coupling contributes to synchronous oscillatory activities of neurons, and considerable progress has been made in defining the molecular composition of gap junction channels. In particular, cloning and functional expression of gap junction proteins (connexins (Cx)) from zebrafish retina have shown that this part of the brain possesses a high degree of connexin diversity that may account for differential functional properties of electrical synapses. Here, we report the cloning and functional characterization of a new connexin, designated zebrafish Cx52.6 (zfCx52.6). This connexin shows little similarity to known connexins from fish and higher vertebrates. By combining in situ hybridization with Laser Capture Microdissection and RT-PCR, we found that this novel fish connexin is expressed in horizontal cells in the inner nuclear layer of the retina. Functional expression of zfCx52.6 in neuroblastoma cells and Xenopus oocytes led to functional gap junctional channels and, in single oocytes, induced large non-junctional membrane currents indicative of the formation of hemichannels, which were inhibited in reversible fashion by raising extracellular Ca(2+) concentrations.
- Published
- 2004
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25. Molecular evidence for local denervation of paraspinal muscles in failed-back surgery/postdiscotomy syndrome.
- Author
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Zoidl G, Grifka J, Boluki D, Willburger RE, Zoidl C, Krämer J, Dermietzel R, and Faustmann PM
- Subjects
- Aged, Biopsy, Down-Regulation, Humans, Intervertebral Disc Displacement surgery, Lumbar Vertebrae surgery, Male, Muscle, Skeletal metabolism, Muscle, Skeletal pathology, Muscular Atrophy, Spinal pathology, Neurons enzymology, Nitric Oxide Synthase metabolism, Peripheral Nerve Injuries, Syndrome, Laminectomy adverse effects, Low Back Pain etiology, Muscle, Skeletal innervation, Muscular Atrophy, Spinal etiology
- Abstract
A study was performed to analyze whether local denervation of the medial branch of the dorsal ramus of the lumbar spinal nerve occurs in a patient with postoperative failed-back surgery syndrome/postdiscotomy syndrome (FBSS/PDS). We investigated the effect of the loss of innervation of the multifidus muscle on neuronal nitrite oxide synthetase (n-NOS) and endothelial nitrite oxide synthetase (e-NOS) applying realtime RT-PCR and immunohistochemistry. Our study demonstrates a substantial reduction of n-NOS expression, supporting the view that local denervation of the multifidus is involved in the pathology of FBSS. No regulation of e-NOS was detectable. Interestingly, this change is region-specific and does not occur throughout the entire multifidus segment. This result supports the hypothesis that local denervation of the multifidus muscle is involved in the pathology of FBSS/ PDS.
- Published
- 2003
26. Loss of HNF1alpha function in human renal cell carcinoma: frequent mutations in the VHL gene but not the HNF1alpha gene.
- Author
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Lemm I, Lingott A, Pogge v Strandmann E, Zoidl C, Bulman MP, Hattersley AT, Schulz WA, Ebert T, and Ryffel GU
- Subjects
- Adenocarcinoma, Clear Cell pathology, Carcinoma, Renal Cell pathology, Cell Differentiation, DNA Mutational Analysis, DNA, Neoplasm genetics, Exons genetics, Genetic Predisposition to Disease, Hepatocyte Nuclear Factor 1, Hepatocyte Nuclear Factor 1-alpha, Hepatocyte Nuclear Factor 1-beta, Humans, Kidney Neoplasms pathology, Neoplasm Proteins biosynthesis, Neoplasm Proteins deficiency, Neoplasm Proteins physiology, Polymorphism, Single-Stranded Conformational, Proteins physiology, Reverse Transcriptase Polymerase Chain Reaction, Sequence Analysis, DNA, Transcription Factors biosynthesis, Transcription Factors genetics, Transcription, Genetic, Tumor Cells, Cultured, Von Hippel-Lindau Tumor Suppressor Protein, Adenocarcinoma, Clear Cell genetics, Carcinoma, Renal Cell genetics, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Genes, Tumor Suppressor, Kidney Neoplasms genetics, Ligases, Neoplasm Proteins genetics, Nuclear Proteins, Proteins genetics, Transcription Factors deficiency, Tumor Suppressor Proteins, Ubiquitin-Protein Ligases
- Abstract
Human renal cell carcinoma (RCC) is a common malignant disease of the kidney characterized by dedifferentiation of renal epithelial cells. Our previous experiments showed that most RCCs have a loss of function of the tissue-specific transcription factor hepatocyte nuclear factor (HNF) 1alpha. Detailed analyses of the 10 exons encoding HNF1alpha in 32 human RCCs by single-strand conformation polymorphism analysis and direct DNA sequencing revealed no tumor-associated mutation, whereas with the same probes we frequently found mutations in the von Hippel-Lindau tumor suppressor gene. No mutation leading to loss of HNF1alpha function was detected by analyzing the integrity of the HNF1alpha transcripts in the RNA derived from RCCs by the protein truncation test. Investigating human RCC cell lines by western blotting and gel retardation assays showed a dramatic loss in the expression of the tissue-specific transcription factor HNF1alpha in eight of 10 cell lines. As the HNF1alpha-related transcription factor HNF1beta was expressed in all these tumor cell lines, the loss of HNF1alpha expression was a specific event and was maintained in RCC cell lines. The loss of HNF1alpha expression in RCC cell lines on the RNA level was confirmed by reverse transcription polymerase chain reaction. We propose that tumor-associated mutations in the HNF1alpha gene do not occur in human RCC and that the loss of function is partially due to a transcriptional inactivation of the HNF1alpha gene.
- Published
- 1999
27. P0 is constitutively expressed in the rat neural crest and embryonic nerves and is negatively and positively regulated by axons to generate non-myelin-forming and myelin-forming Schwann cells, respectively.
- Author
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Lee M, Brennan A, Blanchard A, Zoidl G, Dong Z, Tabernero A, Zoidl C, Dent MA, Jessen KR, and Mirsky R
- Subjects
- Animals, Animals, Newborn physiology, Cell Division, Cell Line, Cells, Cultured, Embryo, Mammalian physiology, Embryonic and Fetal Development, Myelin P0 Protein genetics, Myelin P0 Protein metabolism, RNA, Messenger metabolism, Rats embryology, Rats, Sprague-Dawley, Schwann Cells cytology, Signal Transduction, Axons physiology, Embryo, Mammalian metabolism, Myelin P0 Protein physiology, Myelin Sheath ultrastructure, Nervous System embryology, Neural Crest metabolism, Schwann Cells ultrastructure
- Abstract
We show that in the rat, the major gene of PNS myelin, P0, is expressed long before myelination in the neural crest, Schwann cell precursors, and embryonic Schwann cells irrespective of whether they will myelinate or not. This myelin-independent P0 expression is constitutive and likely to serve as a specific marker for the Schwann cell lineage. The much higher P0 expression accompanying myelination is therefore not new gene expression but strong up-regulation of preexisting basal levels. We provide new evidence that the up-regulation to myelination-related levels depends on positive extrinsic signals and therefore does not represent a constitutive phenotype. P0 mRNA is not detectable in mature non-myelin-forming Schwann cells of the sympathetic trunk, but is detectable after transection, indicating that there is a P0-inhibitory signal associated with mature unmyelinated axons. Thus, the regulation of the P0 gene is complex, encompassing extrinsically signaled amplification superimposed on a highly lineage-specific and constitutive basal expression.
- Published
- 1997
- Full Text
- View/download PDF
28. Regulation and function of the tissue-specific transcription factor HNF1 alpha (LFB1) during Xenopus development.
- Author
-
Weber H, Strandmann EP, Holewa B, Bartkowski S, Zapp D, Zoidl C, and Ryffel GU
- Subjects
- Animals, Base Sequence, Binding Sites genetics, DNA genetics, DNA metabolism, Dimerization, Gene Expression Regulation, Developmental, Hepatocyte Nuclear Factor 1, Hepatocyte Nuclear Factor 1-alpha, Hepatocyte Nuclear Factor 1-beta, Hydro-Lyases genetics, Hydro-Lyases metabolism, Molecular Structure, Promoter Regions, Genetic, Tissue Distribution, Transcription Factors chemistry, Transcription Factors metabolism, Xenopus metabolism, Xenopus Proteins, DNA-Binding Proteins, Nuclear Proteins, Transcription Factors genetics, Xenopus embryology, Xenopus genetics
- Abstract
We review the data available on the structure, developmental appearance and embryonic regulation of the tissue-specific transcription factor HNF1 alpha (LFB1) in Xenopus. The expression of the HNF1 alpha gene starts early in embryogenesis shortly after mid-blastula transition and the protein accumulates in the region of the embryo where liver, pronephros and gut--tissues that contain HNF1 alpha in the adult--are developing. The cofactor DCoH, known to stabilize dimer formation of HNF1 alpha, is present as a maternal factor in the egg and has a partially distinct tissue distribution compared to HNF1 alpha. This implies that DCoH does not only modulate HNF1 alpha dimerization but may also cooperate with other transcription factors. By injecting HNF1 alpha promoter CAT constructs into fertilized Xenopus eggs we obtained activation of the injected gene restricted to the region of the developing larvae expressing endogenous HNF1 alpha. Deletion analysis allowed to define the OZ-element that is essential for embryonic activation. This element also occurs in other promoters activated at mid-blastula transition in the embryo and interacts with the maternal factor OZ-1. As the HNF1 alpha promoter also contains functional binding sites for HNF4 and HNF1, we postulate that all of these transcription factors contribute to the cascade leading to proper embryonic activation of the HNF1 alpha gene.
- Published
- 1996
29. A highly specific and sensitive monoclonal antibody detecting histidine-tagged recombinant proteins.
- Author
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Pogge von Strandmann E, Zoidl C, Nakhei H, Holewa B, Pogge von Strandmann R, Lorenz P, Klein-Hitpass L, and Ryffel GU
- Subjects
- Amino Acid Sequence, Animals, Base Sequence, Blotting, Western, Hepatocyte Nuclear Factor 4, Histidine isolation & purification, Immunohistochemistry, Molecular Sequence Data, Oligodeoxyribonucleotides, Phosphoproteins chemistry, Phosphoproteins immunology, Recombinant Proteins chemistry, Recombinant Proteins immunology, Transcription Factors chemistry, Transcription Factors immunology, Xenopus, Antibodies, Monoclonal immunology, DNA-Binding Proteins, Histidine immunology, Phosphoproteins isolation & purification, Recombinant Proteins isolation & purification, Transcription Factors isolation & purification
- Published
- 1995
- Full Text
- View/download PDF
30. Lowered amounts of the tissue-specific transcription factor LFB1 (HNF1) correlate with decreased levels of glutathione S-transferase alpha messenger RNA in human renal cell carcinoma.
- Author
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Clairmont A, Ebert T, Weber H, Zoidl C, Eickelmann P, Schulz WA, Sies H, and Ryffel GU
- Subjects
- Antibodies, Monoclonal, Antibody Specificity, Base Sequence, Binding Sites, Carcinoma, Renal Cell enzymology, DNA-Binding Proteins genetics, DNA-Binding Proteins physiology, Hepatocyte Nuclear Factor 1, Hepatocyte Nuclear Factor 1-alpha, Hepatocyte Nuclear Factor 1-beta, Humans, Kidney metabolism, Kidney physiology, Kidney Neoplasms enzymology, Molecular Sequence Data, Promoter Regions, Genetic genetics, Promoter Regions, Genetic physiology, Transcription Factors genetics, Carcinoma, Renal Cell genetics, Carcinoma, Renal Cell metabolism, Glutathione Transferase genetics, Glutathione Transferase metabolism, Kidney Neoplasms genetics, Kidney Neoplasms metabolism, Nuclear Proteins, RNA, Messenger metabolism, Transcription Factors metabolism
- Abstract
Human renal cell carcinoma is characterized by the loss of differentiation markers such as glutathione S-transferase alpha (GST-alpha). In this paper we show that the promoter of a GST-alpha gene contains a functional binding site for the cell-specific transcription factor LFB1 (HNF1). To investigate the potential role of LFB1 in the down-regulation of GST-alpha expression, we have compared the amount and the binding activity of the LFB1 protein between normal kidney and tumor tissue. By Western analysis and gel retardation assay using a monoclonal antibody specific for LFB1 we show that in 11 of 14 carcinomas the amount of LFB1 is clearly reduced compared to the corresponding normal tissue and that in all 14 renal carcinomas LFB1 binding activity is diminished. As in the same samples the abundance of GST-alpha mRNA is lower than in the normal tissue, we postulate that the loss of LFB1 binding activity might be responsible for the decreased expression of the GST-alpha gene in renal cell carcinoma.
- Published
- 1994
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