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Molecular Mechanisms of Synaptic Vesicle Priming by Munc13 and Munc18.
Lai, Ying; Choi, Ucheor B; Leitz, Jeremy; Rhee, Hong Jun; Lee, Choongku; Altas, Bekir; Zhao, Minglei; Pfuetzner, Richard A; Wang, Austin L; Brose, Nils; Rhee, JeongSeop; Brunger, Axel T.
Afiliación
  • Lai Y; 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
  • Choi UB; 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
  • Leitz J; 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
  • Rhee HJ; Department of Molecular Neurobiology, Max Planck Institute for Experimental Medicine, 37075 Göttingen, Germany.
  • Lee C; Department of Molecular Neurobiology, Max Planck Institute for Experimental Medicine, 37075 Göttingen, Germany.
  • Altas B; Department of Molecular Neurobiology, Max Planck Institute for Experimental Medicine, 37075 Göttingen, Germany.
  • Zhao M; 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
  • Pfuetzner RA; 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
  • Wang AL; 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
  • Brose N; Department of Molecular Neurobiology, Max Planck Institute for Experimental Medicine, 37075 Göttingen, Germany.
  • Rhee J; Department of Molecular Neurobiology, Max Planck Institute for Experimental Medicine, 37075 Göttingen, Germany.
  • Brunger AT; 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
Neuron ; 95(3): 591-607.e10, 2017 Aug 02.
Article en En | MEDLINE | ID: mdl-28772123
ABSTRACT
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 Ca2+-triggered amplitude and achieves Ca2+ 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vesículas Sinápticas / Neurotransmisores / Péptidos y Proteínas de Señalización Intracelular / Proteínas SNARE / Proteínas Munc18 / Exocitosis / Proteínas del Tejido Nervioso Límite: Animals Idioma: En Revista: Neuron Asunto de la revista: NEUROLOGIA Año: 2017 Tipo del documento: Article
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vesículas Sinápticas / Neurotransmisores / Péptidos y Proteínas de Señalización Intracelular / Proteínas SNARE / Proteínas Munc18 / Exocitosis / Proteínas del Tejido Nervioso Límite: Animals Idioma: En Revista: Neuron Asunto de la revista: NEUROLOGIA Año: 2017 Tipo del documento: Article