Differential SNARE chaperoning by Munc13-1 and Munc18-1 dictates fusion pore fate at the release site.

The regulated release of chemical messengers is crucial for cell-to-cell communication; abnormalities in which impact coordinated human body function. During vesicular secretion, multiple SNARE complexes assemble at the release site, leading to fusion pore opening. How membrane fusion regulators act on heterogeneous SNARE populations to assemble fusion pores in a timely and synchronized manner, is unknown.

Synaptobrevin2 monomers and dimers differentially engage to regulate the functional trans-SNARE assembly.

The precise cell-to-cell communication relies on SNARE-catalyzed membrane fusion. Among ∼70 copies of synaptobrevin2 (syb2) in synaptic vesicles, only ∼3 copies are sufficient to facilitate the fusion process at the presynaptic terminal. It is unclear what dictates the number of SNARE complexes that constitute the fusion pore assembly.

α-Synuclein kinetically regulates the nascent fusion pore dynamics.

α-Synuclein (α-syn) is central to the pathogenesis of Parkinson's disease (PD), in which its nonfunctional oligomers accumulate and result in abnormal neurotransmission. The normal physiological function of this intrinsically disordered protein is still unclear. Although several previous studies demonstrated α-syn's role in various membrane fusion steps, they produced conflicting outcomes regarding vesicular secretion.