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Pesquisa : D12.776.157.530.400.875.100 [Categoria DeCS]
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  1 / 99 MEDLINE  
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[PMID]:28213447
[Au] Autor:Hill A; Zheng X; Li X; McKinney R; Dickman D; Ben-Shahar Y
[Ad] Endereço:Department of Biology, Washington University in St. Louis, St. Louis, Missouri 63130.
[Ti] Título:The Postsynaptic DEG/ENaC Channel Contributes to Excitatory Neurotransmission.
[So] Source:J Neurosci;37(12):3171-3180, 2017 Mar 22.
[Is] ISSN:1529-2401
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The protein family of degenerin/epithelial sodium channels (DEG/ENaCs) is composed of diverse animal-specific, non-voltage-gated ion channels that play important roles in regulating cationic gradients across epithelial barriers. Some family members are also enriched in neural tissues in both vertebrates and invertebrates. However, the specific neurophysiological functions of most DEG/ENaC-encoding genes remain poorly understood. The fruit fly is an excellent model for deciphering the functions of DEG/ENaC genes because its genome encodes an exceptionally large number of DEG/ENaC subunits termed ( ) Here we demonstrate that contributes specifically to the postsynaptic modulation of excitatory synaptic transmission at the larval neuromuscular junction. Electrophysiological data indicate that the function of in muscle is necessary for normal postsynaptic responsivity to neurotransmitter release and for normal coordinated larval movement. The mutation does not affect gross synaptic morphology and ultrastructure, which indicates that the observed phenotypes are likely due to defects in glutamate receptor function. Together, our data indicate that DEG/ENaC ion channels play a fundamental role in the postsynaptic regulation of excitatory neurotransmission. Members of the degenerin/epithelial sodium channel (DEG/ENaC) family are broadly expressed in epithelial and neuronal tissues. To date, the neurophysiological functions of most family members remain unknown. Here, by using the power of genetics in combination with electrophysiological and behavioral approaches, we demonstrate that the DEG/ENaC-encoding gene contributes to baseline neurotransmission, possibly via the modulation of postsynaptic glutamate receptor functionality.
[Mh] Termos MeSH primário: Proteínas de Drosophila/fisiologia
Drosophila/fisiologia
Potenciais Pós-Sinápticos Excitadores/fisiologia
Ativação do Canal Iônico/fisiologia
Canais Iônicos/fisiologia
Junção Neuromuscular/fisiologia
Sódio/metabolismo
[Mh] Termos MeSH secundário: Animais
Células Cultivadas
Canais de Sódio Degenerina/fisiologia
Canais Epiteliais de Sódio/fisiologia
Transmissão Sináptica/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Degenerin Sodium Channels); 0 (Drosophila Proteins); 0 (Epithelial Sodium Channels); 0 (Ion Channels); 0 (PPK29 protein, Drosophila); 9NEZ333N27 (Sodium)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171018
[Lr] Data última revisão:
171018
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170219
[St] Status:MEDLINE
[do] DOI:10.1523/JNEUROSCI.3850-16.2017


  2 / 99 MEDLINE  
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[PMID]:25053538
[Au] Autor:Schafer WR
[Ad] Endereço:Cell Biology Division, MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK, wschafer@mrc-lmb.cam.ac.uk.
[Ti] Título:Mechanosensory molecules and circuits in C. elegans.
[So] Source:Pflugers Arch;467(1):39-48, 2015 Jan.
[Is] ISSN:1432-2013
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Mechanosensory neurons, whose activity is controlled by mechanical force, underlie the senses of touch, hearing, and proprioception, yet despite their importance, the molecular basis of mechanotransduction is poorly understood. Genetic studies in Caenorhabditis elegans have provided a useful approach for identifying potential components of mechanotransduction complexes that might be conserved in more complex organisms. This review describes the mechanosensory systems of C. elegans, including the sensory neurons and circuitry involved in body touch, nose touch, and proprioception. In addition, the roles of genes encoding known and potential mechanosensory receptors, including members of the broadly conserved transient receptor potential (TRP) and degerin/epithelial Na(+) channel (DEG/ENaC) channel families, are discussed.
[Mh] Termos MeSH primário: Proteínas de Caenorhabditis elegans/metabolismo
Caenorhabditis elegans/fisiologia
Mecanorreceptores/fisiologia
Mecanotransdução Celular/fisiologia
Propriocepção/fisiologia
Tato/fisiologia
[Mh] Termos MeSH secundário: Animais
Canais de Sódio Degenerina/metabolismo
Modelos Biológicos
Canais de Receptores Transientes de Potencial/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Caenorhabditis elegans Proteins); 0 (Degenerin Sodium Channels); 0 (Transient Receptor Potential Channels)
[Em] Mês de entrada:1509
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140724
[St] Status:MEDLINE
[do] DOI:10.1007/s00424-014-1574-3


  3 / 99 MEDLINE  
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[PMID]:25456135
[Au] Autor:Gorczyca DA; Younger S; Meltzer S; Kim SE; Cheng L; Song W; Lee HY; Jan LY; Jan YN
[Ad] Endereço:Neuroscience Graduate Program, University of California San Francisco, San Francisco, CA 94158, USA; Departments of Physiology, Biochemistry, and Biophysics, University of California San Francisco, Howard Hughes Medical Institute, San Francisco, CA 94158, USA.
[Ti] Título:Identification of Ppk26, a DEG/ENaC Channel Functioning with Ppk1 in a Mutually Dependent Manner to Guide Locomotion Behavior in Drosophila.
[So] Source:Cell Rep;9(4):1446-58, 2014 Nov 20.
[Is] ISSN:2211-1247
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A major gap in our understanding of sensation is how a single sensory neuron can differentially respond to a multitude of different stimuli (polymodality), such as propio- or nocisensation. The prevailing hypothesis is that different stimuli are transduced through ion channels with diverse properties and subunit composition. In a screen for ion channel genes expressed in polymodal nociceptive neurons, we identified Ppk26, a member of the trimeric degenerin/epithelial sodium channel (DEG/ENaC) family, as being necessary for proper locomotion behavior in Drosophila larvae in a mutually dependent fashion with coexpressed Ppk1, another member of the same family. Mutants lacking Ppk1 and Ppk26 were defective in mechanical, but not thermal, nociception behavior. Mutants of Piezo, a channel involved in mechanical nociception in the same neurons, did not show a defect in locomotion, suggesting distinct molecular machinery for mediating locomotor feedback and mechanical nociception.
[Mh] Termos MeSH primário: Comportamento Animal
Canais de Sódio Degenerina/metabolismo
Proteínas de Drosophila/metabolismo
Drosophila melanogaster/fisiologia
Canais Epiteliais de Sódio/metabolismo
Locomoção
Canais de Sódio/metabolismo
[Mh] Termos MeSH secundário: Animais
Membrana Celular/metabolismo
Dendritos/metabolismo
Mutação/genética
Nociceptividade
Ligação Proteica
Subunidades Proteicas/metabolismo
Temperatura Ambiente
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Degenerin Sodium Channels); 0 (Drosophila Proteins); 0 (Epithelial Sodium Channels); 0 (PPK26 protein, Drosophila); 0 (Ppk1 protein, Drosophila); 0 (Protein Subunits); 0 (Sodium Channels)
[Em] Mês de entrada:1507
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:141203
[St] Status:MEDLINE


  4 / 99 MEDLINE  
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[PMID]:25454784
[Au] Autor:Mauthner SE; Hwang RY; Lewis AH; Xiao Q; Tsubouchi A; Wang Y; Honjo K; Skene JH; Grandl J; Tracey WD
[Ad] Endereço:University Program in Genetics and Genomics, Duke University Medical Center, Duke University, Durham, NC 27710, USA.
[Ti] Título:Balboa binds to pickpocket in vivo and is required for mechanical nociception in Drosophila larvae.
[So] Source:Curr Biol;24(24):2920-5, 2014 Dec 15.
[Is] ISSN:1879-0445
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The Drosophila gene pickpocket (ppk) encodes an ion channel subunit of the degenerin/epithelial sodium channel (DEG/ENaC) family. PPK is specifically expressed in nociceptive, class IV multidendritic (md) neurons and is functionally required for mechanical nociception responses. In this study, in a genome-wide genetic screen for other ion channel subunits required for mechanical nociception, we identify a gene that we name balboa (also known as CG8546, ppk26). Interestingly, the balboa locus encodes a DEG/ENaC ion channel subunit highly similar in amino acid sequence to PPK. Moreover, laser-capture isolation of RNA from larval neurons and microarray analyses reveal that balboa is also highly enriched in nociceptive neurons. The requirement for Balboa and PPK in mechanical nociception behaviors and their specific expression in larval nociceptors led us to hypothesize that these DEG/ENaC subunits form an ion channel complex in vivo. In nociceptive neurons, Balboa::GFP proteins distribute uniformly throughout dendrites but remarkably localize to discrete foci when ectopically expressed in other neuron subtypes (where PPK is not expressed). Indeed, ectopically coexpressing ppk transforms this punctate Balboa::GFP expression pattern to the uniform distribution observed in its native cell type. Furthermore, ppk-RNAi in class IV neurons alters the broad Balboa::GFP pattern to a punctate distribution. Interestingly, this interaction is mutually codependent as balboa-RNAi eliminates Venus::PPK from the sensory dendrites of nociceptors. Finally, using a GFP-reconstitution approach in transgenic larvae, we directly detect in vivo physical interactions among PPK and Balboa subunits. Combined, our results indicate a critical mechanical nociception function for heteromeric PPK and Balboa channels in vivo.
[Mh] Termos MeSH primário: Proteínas de Drosophila/genética
Drosophila melanogaster/fisiologia
Canais Epiteliais de Sódio/genética
Nociceptividade
Canais de Sódio/genética
[Mh] Termos MeSH secundário: Animais
Animais Geneticamente Modificados/genética
Animais Geneticamente Modificados/crescimento & desenvolvimento
Animais Geneticamente Modificados/fisiologia
Canais de Sódio Degenerina/genética
Canais de Sódio Degenerina/metabolismo
Dendritos/metabolismo
Proteínas de Drosophila/metabolismo
Drosophila melanogaster/genética
Drosophila melanogaster/crescimento & desenvolvimento
Canais Epiteliais de Sódio/metabolismo
Larva/fisiologia
Análise de Sequência com Séries de Oligonucleotídeos
Análise de Sequência de Proteína
Canais de Sódio/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Degenerin Sodium Channels); 0 (Drosophila Proteins); 0 (Epithelial Sodium Channels); 0 (PPK26 protein, Drosophila); 0 (Ppk1 protein, Drosophila); 0 (Sodium Channels)
[Em] Mês de entrada:1508
[Cu] Atualização por classe:161019
[Lr] Data última revisão:
161019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:141203
[St] Status:MEDLINE


  5 / 99 MEDLINE  
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[PMID]:25312679
[Au] Autor:Assmann M; Kuhn A; Dürrnagel S; Holstein TW; Gründer S
[Ti] Título:The comprehensive analysis of DEG/ENaC subunits in Hydra reveals a large variety of peptide-gated channels, potentially involved in neuromuscular transmission.
[So] Source:BMC Biol;12:84, 2014 Oct 14.
[Is] ISSN:1741-7007
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: It is generally the case that fast transmission at neural synapses is mediated by small molecule neurotransmitters. The simple nervous system of the cnidarian Hydra, however, contains a large repertoire of neuropeptides and it has been suggested that neuropeptides are the principal transmitters of Hydra. An ion channel directly gated by Hydra-RFamide neuropeptides has indeed been identified in Hydra - the Hydra Na+ channel (HyNaC) 2/3/5, which is expressed at the oral side of the tentacle base. Hydra-RFamides are more widely expressed, however, being found in neurons of the head and peduncle region. Here, we explore whether further peptide-gated HyNaCs exist, where in the animal they are expressed, and whether they are all gated by Hydra-RFamides. RESULTS: We report molecular cloning of seven new HyNaC subunits - HyNaC6 to HyNaC12, all of which are members of the DEG/ENaC gene family. In Xenopus oocytes, these subunits assemble together with the four already known subunits into thirteen different ion channels that are directly gated by Hydra-RFamide neuropeptides with high affinity (up to 40 nM). In situ hybridization suggests that HyNaCs are expressed in epitheliomuscular cells at the oral and the aboral side of the tentacle base and at the peduncle. Moreover, diminazene, an inhibitor of HyNaCs, delayed tentacle movement in live Hydra. CONCLUSIONS: Our results show that Hydra has a large variety of peptide-gated ion channels that are activated by a restricted number of related neuropeptides. The existence and expression pattern of these channels, and behavioral effects induced by channel blockers, suggests that Hydra co-opted neuropeptides for fast neuromuscular transmission.
[Mh] Termos MeSH primário: Canais de Sódio Degenerina/fisiologia
Células Epiteliais/metabolismo
Hydra/genética
Neuropeptídeos/fisiologia
Transmissão Sináptica
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Clonagem Molecular
Canais de Sódio Degenerina/genética
Hydra/fisiologia
Hibridização In Situ
Dados de Sequência Molecular
Neurônios/citologia
Neurônios/fisiologia
Oócitos
Filogenia
Alinhamento de Sequência
Sinapses/genética
Sinapses/fisiologia
Xenopus
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Degenerin Sodium Channels); 0 (Neuropeptides); 34388-59-5 (arginylphenylalaninamide)
[Em] Mês de entrada:1509
[Cu] Atualização por classe:151029
[Lr] Data última revisão:
151029
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:141015
[St] Status:MEDLINE
[do] DOI:10.1186/s12915-014-0084-2


  6 / 99 MEDLINE  
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[PMID]:23842738
[Au] Autor:Lefèvre CM; Diakov A; Haerteis S; Korbmacher C; Gründer S; Wiemuth D
[Ad] Endereço:Institute of Physiology, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany.
[Ti] Título:Pharmacological and electrophysiological characterization of the human bile acid-sensitive ion channel (hBASIC).
[So] Source:Pflugers Arch;466(2):253-63, 2014 Feb.
[Is] ISSN:1432-2013
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:The human bile acid-sensitive ion channel (hBASIC) is a cation channel of the degenerin/epithelial Na(+) channel gene family that is expressed in the intestinal tract and can be activated by bile acids. Here, we show that in addition to its sensitivity for bile acids, hBASIC shares further key features with its rat ortholog: it is blocked by extracellular divalent cations, is inhibited by micromolar concentrations of the diarylamidine diminazene, and activated by millimolar concentrations of flufenamic acid. Furthermore, we demonstrate that two major bile acids present in human bile, chenodeoxycholic acid and deoxycholic acid, activate hBASIC in a synergistic manner. In addition, we determined the single-channel properties of hBASIC in outside-out patch clamp recordings, revealing a single-channel conductance of about 11 pS and a high Na(+) selectivity. Deoxycholic acid activates hBASIC in patch clamp recordings mainly by reducing the single-channel closed time. In summary, we provide a thorough functional characterization of hBASIC.
[Mh] Termos MeSH primário: Canais Iônicos Sensíveis a Ácido/fisiologia
Ácidos e Sais Biliares/farmacologia
Canais de Sódio Degenerina/fisiologia
[Mh] Termos MeSH secundário: Canais Iônicos Sensíveis a Ácido/efeitos dos fármacos
Cátions Bivalentes/farmacologia
Canais de Sódio Degenerina/efeitos dos fármacos
Diminazena/farmacologia
Canais Epiteliais de Sódio/efeitos dos fármacos
Canais Epiteliais de Sódio/fisiologia
Ácido Flufenâmico/farmacologia
Seres Humanos
Ativação do Canal Iônico/fisiologia
Técnicas de Patch-Clamp
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (ASIC5 protein, human); 0 (Acid Sensing Ion Channels); 0 (Bile Acids and Salts); 0 (Cations, Divalent); 0 (Degenerin Sodium Channels); 0 (Epithelial Sodium Channels); 60GCX7Y6BH (Flufenamic Acid); Y5G36EEA5Z (Diminazene)
[Em] Mês de entrada:1409
[Cu] Atualização por classe:171005
[Lr] Data última revisão:
171005
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:130712
[St] Status:MEDLINE
[do] DOI:10.1007/s00424-013-1310-4


  7 / 99 MEDLINE  
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[PMID]:24018065
[Au] Autor:Roy S; Boiteux C; Alijevic O; Liang C; Bernèche S; Kellenberger S
[Ad] Endereço:1Department of Pharmacology and Toxicology, University of Lausanne, Rue du Bugnon 27, CH-1005 Lausanne, Switzerland. stephan.kellenberger@unil.ch.
[Ti] Título:Molecular determinants of desensitization in an ENaC/degenerin channel.
[So] Source:FASEB J;27(12):5034-45, 2013 Dec.
[Is] ISSN:1530-6860
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Epithelial Na(+) channel (ENaC)/degenerin family members are involved in mechanosensation, blood pressure control, pain sensation, and the expression of fear. Several of these channel types display a form of desensitization that allows the channel to limit Na(+) influx during prolonged stimulation. We used site-directed mutagenesis and chemical modification, functional analysis, and molecular dynamics simulations to investigate the role of the lower palm domain of the acid-sensing ion channel 1, a member of the ENaC/degenerin family. The lower palm domains of this trimeric channel are arranged around a central vestibule, at ∼20 Šabove the plasma membrane and are covalently linked to the transmembrane channel parts. We show that the lower palm domains approach one another during desensitization. Residues in the palm co-determine the pH dependence of desensitization, its kinetics, and the stability of the desensitized state. Mutations of palm residues impair desensitization by preventing the closing movement of the palm. Overexpression of desensitization-impaired channel mutants in central neurons allowed--in contrast to overexpression of wild type--a sustained signaling response to rapid pH fluctuations. We identify and describe here the function of an important regulatory domain that most likely has a conserved role in ENaC/degenerin channels.
[Mh] Termos MeSH primário: Canais de Sódio Degenerina/metabolismo
Canais Epiteliais de Sódio/metabolismo
Ativação do Canal Iônico
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Canais de Sódio Degenerina/química
Canais de Sódio Degenerina/genética
Canais Epiteliais de Sódio/química
Canais Epiteliais de Sódio/genética
Concentração de Íons de Hidrogênio
Simulação de Dinâmica Molecular
Dados de Sequência Molecular
Mutação Puntual
Estrutura Terciária de Proteína
Ratos
Ratos Sprague-Dawley
Xenopus
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Degenerin Sodium Channels); 0 (Epithelial Sodium Channels)
[Em] Mês de entrada:1402
[Cu] Atualização por classe:131203
[Lr] Data última revisão:
131203
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:130911
[St] Status:MEDLINE
[do] DOI:10.1096/fj.13-230680


  8 / 99 MEDLINE  
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[PMID]:23547934
[Au] Autor:Giraldez T; Domínguez J; Alvarez de la Rosa D
[Ad] Endereço:Research Division, University Hospital N.S. Candelaria, Santa Cruz de Tenerife, Spain. giraldez@ull.es
[Ti] Título:ENaC in the brain--future perspectives and pharmacological implications.
[So] Source:Curr Mol Pharmacol;6(1):44-9, 2013 Mar.
[Is] ISSN:1874-4702
[Cp] País de publicação:United Arab Emirates
[La] Idioma:eng
[Ab] Resumo:The epithelial sodium channel/degenerin (ENaC/deg) family of ion channels is formed by a large number of genes with variable tissue expression patterns and physiological roles. ENaC is a non-voltage gated, constitutively active channel highly selective for sodium. ENaC is formed by three homologous subunits, α, ß and γ, and a fourth subunit (δ) has been found in human and monkeys that can substitute α to form functional channels. The best-characterized role of ENaC is to serve as a rate-limiting step in transepithelial sodium reabsorption in the distal part of the kidney tubule and other tight epithelia. However, ENaC subunits are also found in the peripheral and central nervous system, where their functional roles are only beginning to be understood. In this review, we mainly focus on the putative pathophysiological roles of ENaC channels in the central nervous system and their potential value as drug targets in neurodegenerative disorders and the central control of blood pressure.
[Mh] Termos MeSH primário: Encéfalo/metabolismo
Canais Epiteliais de Sódio/metabolismo
[Mh] Termos MeSH secundário: Canais Iônicos Sensíveis a Ácido/metabolismo
Animais
Sistema Nervoso Central/metabolismo
Canais de Sódio Degenerina/metabolismo
Canais Epiteliais de Sódio/química
Canais Epiteliais de Sódio/genética
Seres Humanos
Subunidades Proteicas/química
Subunidades Proteicas/genética
Subunidades Proteicas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (Acid Sensing Ion Channels); 0 (Degenerin Sodium Channels); 0 (Epithelial Sodium Channels); 0 (Protein Subunits)
[Em] Mês de entrada:1312
[Cu] Atualização por classe:130610
[Lr] Data última revisão:
130610
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:130404
[St] Status:MEDLINE


  9 / 99 MEDLINE  
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[PMID]:23449991
[Au] Autor:Zelle KM; Lu B; Pyfrom SC; Ben-Shahar Y
[Ad] Endereço:Department of Biology, Washington University in St. Louis, St. Louis, Missouri 63130, USA.
[Ti] Título:The genetic architecture of degenerin/epithelial sodium channels in Drosophila.
[So] Source:G3 (Bethesda);3(3):441-50, 2013 Mar.
[Is] ISSN:2160-1836
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Degenerin/epithelial sodium channels (DEG/ENaC) represent a large family of animal-specific membrane proteins. Although the physiological functions of most family members are not known, some have been shown to act as nonvoltage gated, amiloride-sensitive sodium channels. The DEG/ENaC family is exceptionally large in genomes of Drosophila species relative to vertebrates and other insects. To elucidate the evolutionary history of the DEG/ENaC family in Drosophila, we took advantage of the genomic and genetic information available for 12 Drosophila species that represent all the major species groups in the Drosophila clade. We have identified 31 family members (termed pickpocket genes) in Drosophila melanogaster, which can be divided into six subfamilies, which are represented in all 12 species. Structure prediction analyses suggested that some subunits evolved unique structural features in the large extracellular domain, possibly supporting mechanosensory functions. This finding is further supported by experimental data that show that both ppk1 and ppk26 are expressed in multidendritic neurons, which can sense mechanical nociceptive stimuli in larvae. We also identified representative genes from five of the six DEG/ENaC subfamilies in a mosquito genome, suggesting that the core DEG/ENaC subfamilies were already present early in the dipteran radiation. Spatial and temporal analyses of expression patterns of the various pickpocket genes indicated that paralogous genes often show very different expression patterns, possibly indicating that gene duplication events have led to new physiological or cellular functions rather than redundancy. In summary, our analyses support a rapid early diversification of the DEG/ENaC family in Diptera followed by physiological and/or cellular specialization. Some members of the family may have diversified to support the physiological functions of a yet unknown class of ligands.
[Mh] Termos MeSH primário: Canais de Sódio Degenerina/genética
Drosophila melanogaster/genética
Canais Epiteliais de Sódio/genética
Genoma de Inseto
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Culicidae/genética
Proteínas de Drosophila/genética
Proteínas de Drosophila/metabolismo
Drosophila melanogaster/fisiologia
Evolução Molecular
Duplicação Gênica
Perfilação da Expressão Gênica
Variação Genética
Larva/genética
Larva/fisiologia
Mecanotransdução Celular
Proteínas de Membrana/genética
Proteínas de Membrana/metabolismo
Dados de Sequência Molecular
Família Multigênica
Neurônios/fisiologia
Filogenia
Canais de Sódio/genética
Canais de Sódio/metabolismo
Especificidade da Espécie
Sintenia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Degenerin Sodium Channels); 0 (Drosophila Proteins); 0 (Epithelial Sodium Channels); 0 (Membrane Proteins); 0 (Ppk1 protein, Drosophila); 0 (Sodium Channels)
[Em] Mês de entrada:1309
[Cu] Atualização por classe:161025
[Lr] Data última revisão:
161025
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:130302
[St] Status:MEDLINE
[do] DOI:10.1534/g3.112.005272


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[PMID]:23404498
[Au] Autor:Boiko N; Kucher V; Eaton BA; Stockand JD
[Ad] Endereço:Department of Physiology, University of Texas Health Sciences Center, San Antonio, TX 78229, USA.
[Ti] Título:Inhibition of neuronal degenerin/epithelial Na+ channels by the multiple sclerosis drug 4-aminopyridine.
[So] Source:J Biol Chem;288(13):9418-27, 2013 Mar 29.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The voltage-gated K(+) (Kv) channel blocker 4-aminopyridine (4-AP) is used to target symptoms of the neuroinflammatory disease multiple sclerosis (MS). By blocking Kv channels, 4-AP facilitates action potential conduction and neurotransmitter release in presynaptic neurons, lessening the effects of demyelination. Because they conduct inward Na(+) and Ca(2+) currents that contribute to axonal degeneration in response to inflammatory conditions, acid-sensing ion channels (ASICs) contribute to the pathology of MS. Consequently, ASICs are emerging as disease-modifying targets in MS. Surprisingly, as first demonstrated here, 4-AP inhibits neuronal degenerin/epithelial Na(+) (Deg/ENaC) channels, including ASIC and BLINaC. This effect is specific for 4-AP compared with its heterocyclic base, pyridine, and the related derivative, 4-methylpyridine; and akin to the actions of 4-AP on the structurally unrelated Kv channels, dose- and voltage-dependent. 4-AP has differential actions on distinct ASICs, strongly inhibiting ASIC1a channels expressed in central neurons but being without effect on ASIC3, which is enriched in peripheral sensory neurons. The voltage dependence of the 4-AP block and the single binding site for this inhibitor are consistent with 4-AP binding in the pore of Deg/ENaC channels as it does Kv channels, suggesting a similar mechanism of inhibition in these two classes of channels. These findings argue that effects on both Kv and Deg/ENaC channels should be considered when evaluating the actions of 4-AP. Importantly, the current results are consistent with 4-AP influencing the symptoms of MS as well as the course of the disease because of inhibitory actions on Kv and ASIC channels, respectively.
[Mh] Termos MeSH primário: 4-Aminopiridina/farmacologia
Canais de Sódio Degenerina/metabolismo
Canais Epiteliais de Sódio/metabolismo
Esclerose Múltipla/metabolismo
Neurônios/metabolismo
[Mh] Termos MeSH secundário: Animais
Animais Recém-Nascidos
Células CHO
Cricetinae
Drosophila melanogaster
Hipocampo/metabolismo
Concentração Inibidora 50
Camundongos
Camundongos Endogâmicos C57BL
Doenças Neurodegenerativas/metabolismo
Técnicas de Patch-Clamp
Bloqueadores dos Canais de Potássio/farmacologia
Canais de Potássio/metabolismo
Ratos
Ratos Sprague-Dawley
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Degenerin Sodium Channels); 0 (Epithelial Sodium Channels); 0 (Potassium Channel Blockers); 0 (Potassium Channels); BH3B64OKL9 (4-Aminopyridine)
[Em] Mês de entrada:1305
[Cu] Atualização por classe:161202
[Lr] Data última revisão:
161202
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:130214
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M112.449413



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