TY - JOUR
T1 - Synaptotagmin-1 docks secretory vesicles to syntaxin-1/SNAP-25 acceptor complexes
AU - de Wit, Heidi
AU - Walter, Alexander M
AU - Milosevic, Ira
AU - Gulyás-Kovács, Attila
AU - Riedel, Dietmar
AU - Sørensen, Jakob B
AU - Verhage, Matthijs
N1 - Keywords: Animals; Cell Membrane; Chromaffin Cells; Gene Knockout Techniques; Mice; Munc18 Proteins; Secretory Vesicles; Synaptotagmin I; Syntaxin 1
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
U2 - 10.1016/j.cell.2009.07.027
DO - 10.1016/j.cell.2009.07.027
M3 - Journal article
C2 - 19716167
SN - 0092-8674
VL - 138
SP - 935
EP - 946
JO - Cell
JF - Cell
IS - 5
ER -