Synaptotagmin-1 Docks Secretory Vesicles to Syntaxin-1/SNAP-25 Acceptor Complexes | Zendy

Heidi de Wit | Zendy; Alexander M. Walter | Zendy; Ira Milošević | Zendy; Attila Gulyás-Kovács | Zendy; Dietmar Riedel | Zendy; Jakob B. Sørensen | Zendy; Matthijs Verhage | Zendy

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Synaptotagmin-1 Docks Secretory Vesicles to Syntaxin-1/SNAP-25 Acceptor Complexes

Author(s) -

Heidi de Wit,

Alexander M. Walter,

Ira Milošević,

Attila Gulyás-Kovács,

Dietmar Riedel,

Jakob B. Sørensen,

Matthijs Verhage

Publication year - 2009

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2009.07.027

Subject(s) - syntaxin , synaptotagmin 1 , synaptobrevin , biology , syntaxin 3 , vesicle fusion , stx1a , microbiology and biotechnology , exocytosis , munc 18 , snare complex , snap25 , docking (animal) , lipid bilayer fusion , vesicular transport proteins , vesicle , synaptic vesicle , endosome , biochemistry , membrane , medicine , nursing , vacuolar protein sorting , intracellular

Docking, the initial association of secretory vesicles with the plasma membrane, precedes formation of the SNARE complex, which drives membrane fusion. For many years, the molecular identity of the docked state, and especially the vesicular docking protein, has been unknown, as has the link to SNARE complex assembly. Here, using adrenal chromaffin cells, we identify the vesicular docking partner as synaptotagmin-1, the calcium sensor for exocytosis, and SNAP-25 as an essential plasma membrane docking factor, which, together with the previously known docking factors Munc18-1 and syntaxin, form the minimal docking machinery. Moreover, we show that the requirement for Munc18-1 in docking, but not fusion, can be overcome by stabilizing syntaxin/SNAP-25 acceptor complexes. These findings, together with cross-rescue, double-knockout, and electrophysiological data, lead us to propose that vesicles dock when synaptotagmin-1 binds to syntaxin/SNAP-25 acceptor complexes, whereas Munc18-1 is required for the downstream association of synaptobrevin to form fusogenic SNARE complexes.

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