Your browser doesn't support javascript.
loading
Linker mutations reveal the complexity of synaptotagmin 1 action during synaptic transmission.
Liu, Huisheng; Bai, Hua; Xue, Renhao; Takahashi, Hirohide; Edwardson, J Michael; Chapman, Edwin R.
Afiliación
  • Liu H; 1] Howard Hughes Medical Institute and Department of Neuroscience, University of Wisconsin, Madison, Wisconsin, USA. [2] [3].
  • Bai H; 1] Howard Hughes Medical Institute and Department of Neuroscience, University of Wisconsin, Madison, Wisconsin, USA. [2].
  • Xue R; Howard Hughes Medical Institute and Department of Neuroscience, University of Wisconsin, Madison, Wisconsin, USA.
  • Takahashi H; Department of Pharmacology, University of Cambridge, Cambridge, UK.
  • Edwardson JM; Department of Pharmacology, University of Cambridge, Cambridge, UK.
  • Chapman ER; Howard Hughes Medical Institute and Department of Neuroscience, University of Wisconsin, Madison, Wisconsin, USA.
Nat Neurosci ; 17(5): 670-7, 2014 May.
Article en En | MEDLINE | ID: mdl-24657966
The Ca(2+) sensor for rapid synaptic vesicle exocytosis, synaptotagmin 1 (syt), is largely composed of two Ca(2+)-sensing C2 domains, C2A and C2B. We investigated the apparent synergy between the tandem C2 domains by altering the length and rigidity of the linker that connects them. The behavior of the linker mutants revealed a correlation between the ability of the C2 domains to penetrate membranes in response to Ca(2+) and to drive evoked neurotransmitter release in cultured mouse neurons, uncovering a step in excitation-secretion coupling. Using atomic force microscopy, we found that the synergy between these C2 domains involved intra-molecular interactions between them. Thus, syt function is markedly affected by changes in the physical nature of the linker that connects its tandem C2 domains. Moreover, the linker mutations uncoupled syt-mediated regulation of evoked and spontaneous release, revealing that syt also acts as a fusion clamp before the Ca(2+) trigger.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Mutación Puntual / Transmisión Sináptica / Sinaptotagmina I / Neuronas Límite: Animals / Humans Idioma: En Revista: Nat Neurosci Asunto de la revista: NEUROLOGIA Año: 2014 Tipo del documento: Article Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Mutación Puntual / Transmisión Sináptica / Sinaptotagmina I / Neuronas Límite: Animals / Humans Idioma: En Revista: Nat Neurosci Asunto de la revista: NEUROLOGIA Año: 2014 Tipo del documento: Article Pais de publicación: Estados Unidos