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

: Wen PJ, Grenklo S, Arpino G, Tan XY, Liao HS, Heureaux J, Peng SY, Chiang HC, Hamid E, Zhao WD, Shin W, Nareoja T, Evergren E, Jin YH, Karlsson R, Ebert SN, Jin A, Liu AP, Shupliakov O, Wu LG

Publisher: NATURE PUBLISHING GROUP

: 2016

: Nature Communications

: NATURE COMMUNICATIONS

: NAT COMMUN

: ARTN 12604

: 7

: 14

: 2041-1723

DOI: https://doi.org/10.1038/ncomms12604

Vesicle fusion is executed via formation of an Omega-shaped structure (Omega-profile), followed by closure (kiss-and-run) or merging of the Omega-profile into the plasma membrane (full fusion). Although Omega-profile closure limits release but recycles vesicles economically, Omega-profile merging facilitates release but couples to classical endocytosis for recycling. Despite its crucial role in determining exocytosis/endocytosis modes, how Omega-profile merging is mediated is poorly understood in endocrine cells and neurons containing small similar to 30-300 nm 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 Omega-profile merging by providing sufficient plasma membrane tension to shrink the Omega-profile in neuroendocrine chromaffin cells containing similar to 300 nm vesicles. Actin-directed compounds also induce Omega-profile accumulation at lamprey synaptic active zones, suggesting that actin may mediate Omega-profile merging at synapses. These results uncover molecular and biophysical mechanisms underlying Omega-profile merging.