TCB Publications - Abstract

Ying Lai, Jiajie Diao, Yanxin Liu, Yuji Ishitsuka, Zengliu Su, Klaus Schulten, Taekjip Ha, and Yeon-Kyun Shin. Fusion pore formation and expansion induced by Ca2+ and synaptotagmin 1. Proceedings of the National Academy of Sciences, USA, 110:1333-1338, 2013. (PMC: 3557091)

LAI2013 Fusion pore formation and expansion, crucial steps for neurotransmitter release and vesicle recycling in SNARE-dependent vesicle fusion, have not been well studied in vitro due to the lack of a reliable content mixing fusion assay. Using methods detecting the inter-vesicular mixing of small and large cargoes at a single vesicle level, we found that the neuronal SNARE complexes have the capacity to drive membrane hemifusion. However, efficient fusion pore formation and expansion require synaptotagmin 1 and Ca2+. Real- time measurements show that pore expansion detected by content mixing of large DNA cargoes occurs much slower than initial pore formation that transmits small cargoes. Slow pore expansion perhaps provides a time window for vesicles to escape the full collapse fusion pathway via alternative mechanisms such as kiss-and-run. The results also show that complexin 1 stimulates pore expansion significantly, which could put bias between two pathways of vesicle recycling.

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