Vesicle Shrinking and Enlargement Play Opposing Roles in the Release of Exocytotic Contents
Wonchul Shin, Gianvito Arpino, Sathish Thiyagarajan, Rui Su, Lihao Ge, Zachary A. McDargh, Xiaoli Guo, Lisi Wei, Oleg Shupliakov, Albert J. Jin, Ben O’Shaughnessy, Ling‐Gang Wu
Abstract
For decades, two fusion modes were thought to control hormone and transmitter release essential to life; one facilitates release via fusion pore dilation and flattening (full collapse), and the other limits release by closing a narrow fusion pore (kiss-and-run). Using super-resolution stimulated emission depletion (STED) microscopy to visualize fusion modes of dense-core vesicles in neuroendocrine cells, we find that facilitation of release is mediated not by full collapse but by shrink fusion, in which the Ω-profile generated by vesicle fusion shrinks but maintains a large non-dilating pore. We discover that the physiological osmotic pressure of a cell squeezes, but does not dilate, the Ω-profile, which explains why shrink fusion prevails over full collapse. Instead of kiss-and-run, enlarge fusion, in which Ω-profiles grow while maintaining a narrow pore, slows down release. Shrink and enlarge fusion may thus account for diverse hormone and transmitter release kinetics observed in secretory cells, previously interpreted within the full-collapse/kiss-and-run framework.