Peter J. Wen, Staffan Grenklo, Gianvito Arpino, Xinyu Tan, Hsien-Shun Liao, Johanna Heureaux, Shi-Yong Peng, Hsueh-Cheng Chiang, Edaeni Hamid, Wei-Dong Zhao, Wonchul Shin, Tuomas Näreoja, Emma Evergren, Yinghui Jin, Roger Karlsson, Steven N. Ebert, Albert Jin, Allen P. Liu, Oleg Shupliakov & Ling-Gang Wu.

Actin dynamics provides membrane tension to merge fusing vesicles into the plasma membrane

Nature Communications 7, Article number: 12604
doi:10.1038/ncomms12604
 

 

Abstract

Vesicle fusion is executed via formation of an -shaped structure (-profile), followed by closure (kiss-and-run) or merging of the -profile into the plasma membrane (full fusion). Although -profile closure limits release but recycles vesicles economically, -profile merging facilitates release but couples to classical endocytosis for recycling. Despite its crucial role in determining exocytosis/endocytosis modes, how -profile merging is mediated is poorly understood in endocrine cells and neurons containing small ~30–300nm vesicles. Here, using confocal and super-resolution STED imaging, force measurements, pharmacology and gene knockout, we show that dynamic assembly of filamentous actin, involving ATP hydrolysis, N-WASP and formin, mediates -profile merging by providing sufficient plasma membrane tension to shrink the -profile in neuroendocrine chromaffin cells containing ~300nm vesicles. Actin-directed compounds also induce -profile accumulation at lamprey synaptic active zones, suggesting that actin may mediate -profile merging at synapses. These results uncover molecular and biophysical mechanisms underlying -profile merging.