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  1 / 2500 MEDLINE  
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[PMID]:29371650
[Au] Autor:Sheikhbahaei S; Turovsky EA; Hosford PS; Hadjihambi A; Theparambil SM; Liu B; Marina N; Teschemacher AG; Kasparov S; Smith JC; Gourine AV
[Ad] Endereço:Centre for Cardiovascular and Metabolic Neuroscience, Department of Neuroscience, Physiology and Pharmacology, University College London, London, WC1E 6BT, UK.
[Ti] Título:Astrocytes modulate brainstem respiratory rhythm-generating circuits and determine exercise capacity.
[So] Source:Nat Commun;9(1):370, 2018 01 25.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Astrocytes are implicated in modulation of neuronal excitability and synaptic function, but it remains unknown if these glial cells can directly control activities of motor circuits to influence complex behaviors in vivo. This study focused on the vital respiratory rhythm-generating circuits of the preBötzinger complex (preBötC) and determined how compromised function of local astrocytes affects breathing in conscious experimental animals (rats). Vesicular release mechanisms in astrocytes were disrupted by virally driven expression of either the dominant-negative SNARE protein or light chain of tetanus toxin. We show that blockade of vesicular release in preBötC astrocytes reduces the resting breathing rate and frequency of periodic sighs, decreases rhythm variability, impairs respiratory responses to hypoxia and hypercapnia, and dramatically reduces the exercise capacity. These findings indicate that astrocytes modulate the activity of CNS circuits generating the respiratory rhythm, critically contribute to adaptive respiratory responses in conditions of increased metabolic demand and determine the exercise capacity.
[Mh] Termos MeSH primário: Astrócitos/fisiologia
Tronco Encefálico/fisiologia
Periodicidade
Condicionamento Físico Animal/fisiologia
Respiração
[Mh] Termos MeSH secundário: Potenciais de Ação/fisiologia
Adenoviridae/genética
Adenoviridae/metabolismo
Animais
Animais Recém-Nascidos
Astrócitos/citologia
Tronco Encefálico/citologia
Cálcio/metabolismo
Feminino
Regulação da Expressão Gênica
Vetores Genéticos/química
Vetores Genéticos/metabolismo
Hipercapnia/metabolismo
Hipercapnia/fisiopatologia
Hipóxia/metabolismo
Hipóxia/fisiopatologia
Masculino
Bulbo/citologia
Bulbo/fisiologia
Cultura Primária de Células
Ratos
Ratos Sprague-Dawley
Proteínas SNARE/antagonistas & inibidores
Proteínas SNARE/genética
Proteínas SNARE/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., INTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (SNARE Proteins); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180215
[Lr] Data última revisão:
180215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180127
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02723-6


  2 / 2500 MEDLINE  
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[PMID]:29254991
[Au] Autor:Hernández JM; Podbilewicz B
[Ad] Endereço:Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, D-44227 Dortmund, Germany matias.hernandez@mpi-dortmund.mpg.de podbilew@technion.ac.il.
[Ti] Título:The hallmarks of cell-cell fusion.
[So] Source:Development;144(24):4481-4495, 2017 Dec 15.
[Is] ISSN:1477-9129
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Cell-cell fusion is essential for fertilization and organ development. Dedicated proteins known as fusogens are responsible for mediating membrane fusion. However, until recently, these proteins either remained unidentified or were poorly understood at the mechanistic level. Here, we review how fusogens surmount multiple energy barriers to mediate cell-cell fusion. We describe how early preparatory steps bring membranes to a distance of ∼10 nm, while fusogens act in the final approach between membranes. The mechanical force exerted by cell fusogens and the accompanying lipidic rearrangements constitute the hallmarks of cell-cell fusion. Finally, we discuss the relationship between viral and eukaryotic fusogens, highlight a classification scheme regrouping a superfamily of fusogens called Fusexins, and propose new questions and avenues of enquiry.
[Mh] Termos MeSH primário: Adesão Celular/fisiologia
Fusão Celular
Fusão de Membrana/fisiologia
[Mh] Termos MeSH secundário: Animais
Caenorhabditis elegans
Proteínas de Caenorhabditis elegans/metabolismo
Drosophila
Produtos do Gene env/metabolismo
Seres Humanos
Glicoproteínas de Membrana/metabolismo
Mioblastos/metabolismo
Proteínas da Gravidez/metabolismo
Proteínas SNARE/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (AFF-1 protein, C elegans); 0 (Caenorhabditis elegans Proteins); 0 (EFF-1 protein, C elegans); 0 (Gene Products, env); 0 (Membrane Glycoproteins); 0 (Pregnancy Proteins); 0 (SNARE Proteins); 0 (syncytin)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180102
[Lr] Data última revisão:
180102
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171220
[St] Status:MEDLINE
[do] DOI:10.1242/dev.155523


  3 / 2500 MEDLINE  
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[PMID]:28463755
[Au] Autor:Yu S; Melia TJ
[Ad] Endereço:Department of Cell Biology, Yale University School of Medicine, New Haven, CT, United States.
[Ti] Título:The coordination of membrane fission and fusion at the end of autophagosome maturation.
[So] Source:Curr Opin Cell Biol;47:92-98, 2017 Aug.
[Is] ISSN:1879-0410
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The two major objectives of macroautophagy are to sequester cargo away from the cytoplasm and deliver this material for breakdown in the lysosome. Sequestration is complete when the autophagosome membrane undergoes fission to produce separate inner and outer membranes, while delivery into the lysosome requires fusion of the outer autophagosome membrane with the lysosome membrane. Thus, the merging of membranes through fission and fusion underlies each of the pivotal events in macroautophagic clearance. How these merging events are controlled in the cell is poorly understood. Several recent studies however suggest that the two events may be temporally coordinated and rely upon members of the classic membrane fusion SNARE family as well as the autophagy-specific family of Atg8 proteins.
[Mh] Termos MeSH primário: Autofagossomos/metabolismo
Membranas Intracelulares/metabolismo
Lisossomos/metabolismo
Proteínas SNARE/metabolismo
[Mh] Termos MeSH secundário: Animais
Autofagia
Família da Proteína 8 Relacionada à Autofagia/metabolismo
Fusão de Membrana
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Autophagy-Related Protein 8 Family); 0 (SNARE Proteins)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171128
[Lr] Data última revisão:
171128
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


  4 / 2500 MEDLINE  
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[PMID]:28945220
[Au] Autor:Schwarz Y; Zhao N; Kirchhoff F; Bruns D
[Ad] Endereço:Molecular Neurophysiology, Center for Integrative Physiology and Molecular Medicine, Saarland University, Homburg, Germany.
[Ti] Título:Astrocytes control synaptic strength by two distinct v-SNARE-dependent release pathways.
[So] Source:Nat Neurosci;20(11):1529-1539, 2017 Nov.
[Is] ISSN:1546-1726
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Communication between glia cells and neurons is crucial for brain functions, but the molecular mechanisms and functional consequences of gliotransmission remain enigmatic. Here we report that astrocytes express synaptobrevin II and cellubrevin as functionally non-overlapping vesicular SNARE proteins on glutamatergic vesicles and neuropeptide Y-containing large dense-core vesicles, respectively. Using individual null-mutants for Vamp2 (synaptobrevin II) and Vamp3 (cellubrevin), as well as the corresponding compound null-mutant for genes encoding both v-SNARE proteins, we delineate previously unrecognized individual v-SNARE dependencies of astrocytic release processes and their functional impact on neuronal signaling. Specifically, we show that astroglial cellubrevin-dependent neuropeptide Y secretion diminishes synaptic signaling, while synaptobrevin II-dependent glutamate release from astrocytes enhances synaptic signaling. Our experiments thereby uncover the molecular mechanisms of two distinct v-SNARE-dependent astrocytic release pathways that oppositely control synaptic strength at presynaptic sites, elucidating new avenues of communication between astrocytes and neurons.
[Mh] Termos MeSH primário: Astrócitos/secreção
Proteínas SNARE/secreção
Transdução de Sinais/fisiologia
Sinapses/secreção
[Mh] Termos MeSH secundário: Difosfato de Adenosina/farmacologia
Animais
Astrócitos/efeitos dos fármacos
Astrócitos/fisiologia
Células Cultivadas
Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos
Potenciais Pós-Sinápticos Excitadores/fisiologia
Feminino
Masculino
Camundongos
Camundongos Knockout
Camundongos Transgênicos
Técnicas de Cultura de Órgãos
Transdução de Sinais/efeitos dos fármacos
Sinapses/efeitos dos fármacos
Sinapses/fisiologia
Xantinas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (SNARE Proteins); 0 (Xanthines); 61D2G4IYVH (Adenosine Diphosphate); 9PTP4FOI9E (1,3-dipropyl-8-cyclopentylxanthine)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171102
[Lr] Data última revisão:
171102
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170926
[St] Status:MEDLINE
[do] DOI:10.1038/nn.4647


  5 / 2500 MEDLINE  
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[PMID]:28914590
[Au] Autor:Gomi H; Osawa H; Uno R; Yasui T; Hosaka M; Torii S; Tsukise A
[Ad] Endereço:Department of Veterinary Anatomy, College of Bioresource Sciences, Nihon University, Fujisawa, Japan.
[Ti] Título:Canine Salivary Glands: Analysis of Rab and SNARE Protein Expression and SNARE Complex Formation With Diverse Tissue Properties.
[So] Source:J Histochem Cytochem;65(11):637-653, 2017 Nov.
[Is] ISSN:1551-5044
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The comparative structure and expression of salivary components and vesicular transport proteins in the canine major salivary glands were investigated. Histochemical analysis revealed that the morphology of the five major salivary glands-parotid, submandibular, polystomatic sublingual, monostomatic sublingual, and zygomatic glands-was greatly diverse. Immunoblot analysis revealed that expression levels of α-amylase and antimicrobial proteins, such as lysozyme, lactoperoxidase, and lactoferrin, differed among the different glands. Similarly, Rab proteins (Rab3d, Rab11a, Rab11b, Rab27a, and Rab27b) and soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor (SNARE) proteins VAMP4, VAMP8, syntaxin-2, syntaxin-3, syntaxin-4, and syntaxin-6 were expressed at various levels in individual glands. mmunohistochemistry of Rab3d, Rab11b, Rab27b, VAMP4, VAMP8, syntaxin-4, and syntaxin-6 revealed their predominant expression in serous acinar cells, demilunes, and ductal cells. The VAMP4/syntaxin-6 SNARE complex, which is thought to be involved in the maturation of secretory granules in the Golgi field, was found more predominantly in the monostomatic sublingual gland than in the parotid gland. These results suggest that protein expression profiles in canine salivary glands differ among individual glands and reflect the properties of their specialized functions.
[Mh] Termos MeSH primário: Proteínas de Ligação a RNA/metabolismo
Proteínas SNARE/metabolismo
Glândulas Salivares/metabolismo
[Mh] Termos MeSH secundário: Animais
Western Blotting
Cães
Imuno-Histoquímica
Imunoprecipitação
Masculino
Ligação Proteica
Proteínas e Peptídeos Salivares/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA-Binding Proteins); 0 (SNARE Proteins); 0 (Salivary Proteins and Peptides)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171110
[Lr] Data última revisão:
171110
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170916
[St] Status:MEDLINE
[do] DOI:10.1369/0022155417732527


  6 / 2500 MEDLINE  
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[PMID]:28858288
[Au] Autor:Liu X; Seven AB; Xu J; Esser V; Su L; Ma C; Rizo J
[Ad] Endereço:Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
[Ti] Título:Simultaneous lipid and content mixing assays for in vitro reconstitution studies of synaptic vesicle fusion.
[So] Source:Nat Protoc;12(9):2014-2028, 2017 Sep.
[Is] ISSN:1750-2799
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:This protocol describes reconstitution assays to study how the neurotransmitter release machinery triggers Ca -dependent synaptic vesicle fusion. The assays monitor fusion between proteoliposomes containing the synaptic vesicle SNARE synaptobrevin (with or without the Ca sensor synaptotagmin-1) and proteoliposomes initially containing the plasma membrane SNAREs syntaxin-1 and soluble NSF attachment protein (SNAP)-25. Lipid mixing (from fluorescence de-quenching of Marina-Blue-labeled lipids) and content mixing (from development of fluorescence resonance energy transfer (FRET) between phycoerythrin-biotin (PhycoE-Biotin) and Cy5-streptavidin trapped in the two proteoliposome populations) are measured simultaneously to ensure that true, nonleaky membrane fusion is monitored. This protocol is based on a method developed to study yeast vacuolar fusion. In contrast to other protocols used to study the release machinery, this assay incorporates N-ethylmaleimide sensitive factor (NSF) and α-SNAP, which disassemble syntaxin-1 and SNAP-25 heterodimers. As a result, fusion requires Munc18-1, which binds to the released syntaxin-1, and Munc13-1, which, together with Munc18-1, orchestrates SNARE complex assembly. The protocol can be readily adapted to investigation of other types of intracellular membrane fusion by using appropriate alternative proteins. Total time required for one round of the assay is 4 d.
[Mh] Termos MeSH primário: Fusão de Membrana/fisiologia
Modelos Biológicos
Proteínas SNARE/química
Proteínas SNARE/metabolismo
Vesículas Sinápticas/química
Vesículas Sinápticas/metabolismo
[Mh] Termos MeSH secundário: Corantes/química
Corantes/metabolismo
Lipídeos/química
Lipossomos/química
Lipossomos/metabolismo
Transmissão Sináptica
Proteínas de Transporte Vesicular/química
Proteínas de Transporte Vesicular/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Coloring Agents); 0 (Lipids); 0 (Liposomes); 0 (SNARE Proteins); 0 (Vesicular Transport Proteins)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170914
[Lr] Data última revisão:
170914
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170901
[St] Status:MEDLINE
[do] DOI:10.1038/nprot.2017.068


  7 / 2500 MEDLINE  
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[PMID]:28841669
[Au] Autor:Rehman A; Hu SH; Tnimov Z; Whitten AE; King GJ; Jarrott RJ; Norwood SJ; Alexandrov K; Collins BM; Christie MP; Martin JL
[Ad] Endereço:Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, QLD, Australia.
[Ti] Título:The nature of the Syntaxin4 C-terminus affects Munc18c-supported SNARE assembly.
[So] Source:PLoS One;12(8):e0183366, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Vesicular transport of cellular cargo requires targeted membrane fusion and formation of a SNARE protein complex that draws the two apposing fusing membranes together. Insulin-regulated delivery and fusion of glucose transporter-4 storage vesicles at the cell surface is dependent on two key proteins: the SNARE integral membrane protein Syntaxin4 (Sx4) and the soluble regulatory protein Munc18c. Many reported in vitro studies of Munc18c:Sx4 interactions and of SNARE complex formation have used soluble Sx4 constructs lacking the native transmembrane domain. As a consequence, the importance of the Sx4 C-terminal anchor remains poorly understood. Here we show that soluble C-terminally truncated Sx4 dissociates more rapidly from Munc18c than Sx4 where the C-terminal transmembrane domain is replaced with a T4-lysozyme fusion. We also show that Munc18c appears to inhibit SNARE complex formation when soluble C-terminally truncated Sx4 is used but does not inhibit SNARE complex formation when Sx4 is C-terminally anchored (by a C-terminal His-tag bound to resin, by a C-terminal T4L fusion or by the native C-terminal transmembrane domain in detergent micelles). We conclude that the C-terminus of Sx4 is critical for its interaction with Munc18c, and that the reported inhibitory role of Munc18c may be an artifact of experimental design. These results support the notion that a primary role of Munc18c is to support SNARE complex formation and membrane fusion.
[Mh] Termos MeSH primário: Proteínas Munc18/metabolismo
Proteínas Qa-SNARE/metabolismo
Proteínas SNARE/metabolismo
[Mh] Termos MeSH secundário: Ligação Proteica
Proteínas Qa-SNARE/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Munc18 Proteins); 0 (Qa-SNARE Proteins); 0 (SNARE Proteins)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171019
[Lr] Data última revisão:
171019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170826
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0183366


  8 / 2500 MEDLINE  
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[PMID]:28827281
[Au] Autor:Arnold MG; Adhikari P; Kang B; Xu 徐昊 H
[Ad] Endereço:Department of Biological Sciences, University of Southern Mississippi, 118 College Drive, #5018, Hattiesburg, Mississippi 39406, U.S.A.
[Ti] Título:Munc18a clusters SNARE-bearing liposomes prior to -SNARE zippering.
[So] Source:Biochem J;474(19):3339-3354, 2017 Sep 24.
[Is] ISSN:1470-8728
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Sec1-Munc18 (SM) proteins co-operate with SNAREs {SNAP [soluble NSF ( -ethylmaleimide-sensitive factor) attachment protein] receptors} to mediate membrane fusion in eukaryotic cells. Studies of Munc18a/Munc18-1/Stxbp1 in neurotransmission suggest that SM proteins accelerate fusion kinetics primarily by activating the partially zippered -SNARE complex. However, accumulating evidence has argued for additional roles for SM proteins in earlier steps in the fusion cascade. Here, we investigate the function of Munc18a in reconstituted exocytic reactions mediated by neuronal and non-neuronal SNAREs. We show that Munc18a plays a direct role in promoting proteoliposome clustering, underlying vesicle docking during exocytosis. In the three different fusion reactions examined, Munc18a-dependent clustering requires an intact N-terminal peptide (N-peptide) motif in syntaxin that mediates the binary interaction between syntaxin and Munc18a. Importantly, clustering is preserved under inhibitory conditions that abolish both -SNARE complex formation and lipid mixing, indicating that Munc18a promotes membrane clustering in a step that is independent of -SNARE zippering and activation.
[Mh] Termos MeSH primário: Lipossomos/metabolismo
Proteínas Munc18/química
Proteínas Munc18/metabolismo
Proteínas SNARE/metabolismo
[Mh] Termos MeSH secundário: Motivos de Aminoácidos
Animais
Exocitose
Lipossomos/química
Fusão de Membrana
Proteínas Munc18/genética
Proteínas Qa-SNARE/química
Proteínas Qa-SNARE/metabolismo
Proteínas R-SNARE/genética
Proteínas R-SNARE/metabolismo
Ratos
Proteínas SNARE/genética
Proteína 25 Associada a Sinaptossoma/genética
Proteína 25 Associada a Sinaptossoma/metabolismo
Proteína 2 Associada à Membrana da Vesícula/genética
Proteína 2 Associada à Membrana da Vesícula/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Liposomes); 0 (Munc18 Proteins); 0 (Qa-SNARE Proteins); 0 (R-SNARE Proteins); 0 (SNARE Proteins); 0 (Snap25 protein, rat); 0 (Synaptosomal-Associated Protein 25); 0 (Vamp2 protein, rat); 0 (Vamp8 protein, rat); 0 (Vesicle-Associated Membrane Protein 2)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171025
[Lr] Data última revisão:
171025
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170823
[St] Status:MEDLINE
[do] DOI:10.1042/BCJ20170494


  9 / 2500 MEDLINE  
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[PMID]:28821673
[Au] Autor:Park S; Bin NR; Yu B; Wong R; Sitarska E; Sugita K; Ma K; Xu J; Tien CW; Algouneh A; Turlova E; Wang S; Siriya P; Shahid W; Kalia L; Feng ZP; Monnier PP; Sun HS; Zhen M; Gao S; Rizo J; Sugita S
[Ad] Endereço:Divisions of Fundamental Neurobiology and.
[Ti] Título:UNC-18 and Tomosyn Antagonistically Control Synaptic Vesicle Priming Downstream of UNC-13 in .
[So] Source:J Neurosci;37(36):8797-8815, 2017 Sep 06.
[Is] ISSN:1529-2401
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Munc18-1/UNC-18 is believed to prime SNARE-mediated membrane fusion, yet the underlying mechanisms remain enigmatic. Here, we examine how potential gain-of-function mutations of Munc18-1/UNC-18 affect locomotory behavior and synaptic transmission, and how Munc18-1-mediated priming is related to Munc13-1/UNC-13 and Tomosyn/TOM-1, positive and negative SNARE regulators, respectively. We show that a Munc18-1(P335A)/UNC-18(P334A) mutation leads to significantly increased locomotory activity and acetylcholine release in , as well as enhanced synaptic neurotransmission in cultured mammalian neurons. Importantly, similar to null mutants, ( ) mutants partially bypass the requirement of UNC-13. Moreover, ( ) and null mutations confer a strong synergy in suppressing the phenotypes of mutants. Through biochemical experiments, we demonstrate that Munc18-1(P335A) exhibits enhanced activity in SNARE complex formation as well as in binding to the preformed SNARE complex, and partially bypasses the Munc13-1 requirement in liposome fusion assays. Our results indicate that Munc18-1/UNC-18 primes vesicle fusion downstream of Munc13-1/UNC-13 by templating SNARE complex assembly and acts antagonistically with Tomosyn/TOM-1. At presynaptic sites, SNARE-mediated membrane fusion is tightly regulated by several key proteins including Munc18/UNC-18, Munc13/UNC-13, and Tomosyn/TOM-1. However, how these proteins interact with each other to achieve the precise regulation of neurotransmitter release remains largely unclear. Using as an model, we found that a gain-of-function mutant of UNC-18 increases locomotory activity and synaptic acetylcholine release, that it partially bypasses the requirement of UNC-13 for release, and that this bypass is synergistically augmented by the lack of TOM-1. We also elucidated the biochemical basis for the gain-of-function caused by this mutation. Thus, our study provides novel mechanistic insights into how Munc18/UNC-18 primes synaptic vesicle release and how this protein interacts functionally with Munc13/UNC-13 and Tomosyn/TOM-1.
[Mh] Termos MeSH primário: Proteínas de Caenorhabditis elegans/metabolismo
Caenorhabditis elegans/fisiologia
Proteínas de Transporte/metabolismo
Locomoção/fisiologia
Fosfoproteínas/metabolismo
Proteínas SNARE/metabolismo
Transmissão Sináptica/fisiologia
Proteínas de Transporte Vesicular/metabolismo
[Mh] Termos MeSH secundário: Animais
Proteínas de Caenorhabditis elegans/genética
Proteínas de Transporte/genética
Mutação/genética
Neurônios
Fosfoproteínas/genética
Vesículas Sinápticas/metabolismo
Proteínas de Transporte Vesicular/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Caenorhabditis elegans Proteins); 0 (Carrier Proteins); 0 (Phosphoproteins); 0 (SNARE Proteins); 0 (Unc-18 protein, C elegans); 0 (Vesicular Transport Proteins); 0 (phorbol ester binding protein)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170925
[Lr] Data última revisão:
170925
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170820
[St] Status:MEDLINE
[do] DOI:10.1523/JNEUROSCI.0338-17.2017


  10 / 2500 MEDLINE  
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[PMID]:28772123
[Au] Autor:Lai Y; Choi UB; Leitz J; Rhee HJ; Lee C; Altas B; Zhao M; Pfuetzner RA; Wang AL; Brose N; Rhee J; Brunger AT
[Ad] Endereço:Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305, USA; Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA; Department of Structural Biology, Stanford University, Stanford, CA 94305, USA; Department of Photon Science
[Ti] Título:Molecular Mechanisms of Synaptic Vesicle Priming by Munc13 and Munc18.
[So] Source:Neuron;95(3):591-607.e10, 2017 Aug 02.
[Is] ISSN:1097-4199
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Munc13 catalyzes the transit of syntaxin from a closed complex with Munc18 into the ternary SNARE complex. Here we report a new function of Munc13, independent of Munc18: it promotes the proper syntaxin/synaptobrevin subconfiguration during assembly of the ternary SNARE complex. In cooperation with Munc18, Munc13 additionally ensures the proper syntaxin/SNAP-25 subconfiguration. In a reconstituted fusion assay with SNAREs, complexin, and synaptotagmin, inclusion of both Munc13 and Munc18 quadruples the Ca -triggered amplitude and achieves Ca sensitivity at near-physiological concentrations. In Munc13-1/2 double-knockout neurons, expression of a constitutively open mutant of syntaxin could only minimally restore neurotransmitter release relative to Munc13-1 rescue. Together, the physiological functions of Munc13 may be related to regulation of proper SNARE complex assembly.
[Mh] Termos MeSH primário: Exocitose/fisiologia
Peptídeos e Proteínas de Sinalização Intracelular/metabolismo
Proteínas Munc18/metabolismo
Proteínas do Tecido Nervoso/metabolismo
Neurotransmissores/metabolismo
Proteínas SNARE/metabolismo
Vesículas Sinápticas/metabolismo
[Mh] Termos MeSH secundário: Animais
Células Cultivadas
Peptídeos e Proteínas de Sinalização Intracelular/genética
Camundongos
Proteínas do Tecido Nervoso/genética
Neurônios/fisiologia
Transmissão Sináptica/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Intracellular Signaling Peptides and Proteins); 0 (Munc18 Proteins); 0 (Nerve Tissue Proteins); 0 (Neurotransmitter Agents); 0 (SNARE Proteins); 0 (Unc13a protein, mouse); 0 (Unc13b protein, mouse)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170914
[Lr] Data última revisão:
170914
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170804
[St] Status:MEDLINE



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