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Juxtamembrane tryptophans of synaptobrevin 2 control the process of membrane fusion

2012; Wiley; Volume: 587; Issue: 1 Linguagem: Inglês

10.1016/j.febslet.2012.11.002

1873-3468

Qinghua Fang, Ying Zhao, Manfred Lindau,

Erythrocyte Function and Pathophysiology

Synaptobrevin 2 (Syb2), syntaxin (Sx1A), and SNAP‐25, generate a force to induce fusion pore formation. The v‐SNARE, Syb2, is anchored to the vesicle membrane by a single transmembrane domain. Here we show that 2 tryptophans (W89/W90) located in the juxtamembrane domain of Syb2, which stabilize the transmembrane (TM) domain position, control the ratio of spontaneous vs. stimulated membrane fusion events in chromaffin cells. Changing the 2 hydrophobic tryptophans to neutral alanines promotes spontaneous membrane fusion, faster transmitter release kinetics and complete release from individual vesicles. The results indicate that the two tryptophans act as a fusion clamp making fusion stimulus‐dependent.