Vesicle Shrinking and Enlargement Play Opposing Roles in the Release of Exocytotic Contents
Wonchul Shin,
Gianvito Arpino,
Sathish Thiyagarajan,
Rui Su,
Lihao Ge,
Zachary McDargh,
Xiaoli Guo,
Lisi Wei,
Oleg Shupliakov,
Albert Jin,
Ben O’Shaughnessy,
Ling-Gang Wu
Affiliations
Wonchul Shin
National Institute of Neurological Disorders and Stroke, 35 Convent Dr., Bldg. 35, Rm. 2B-1012, Bethesda, MD 20892, USA
Gianvito Arpino
National Institute of Neurological Disorders and Stroke, 35 Convent Dr., Bldg. 35, Rm. 2B-1012, Bethesda, MD 20892, USA; Department of Neuroscience, Karolinska Institutet, 17177 Stockholm, Sweden
Sathish Thiyagarajan
Department of Chemical Engineering, Columbia University, New York, NY 10027, USA
Rui Su
Department of Chemical Engineering, Columbia University, New York, NY 10027, USA
Lihao Ge
National Institute of Neurological Disorders and Stroke, 35 Convent Dr., Bldg. 35, Rm. 2B-1012, Bethesda, MD 20892, USA
Zachary McDargh
Department of Chemical Engineering, Columbia University, New York, NY 10027, USA
Xiaoli Guo
National Institute of Neurological Disorders and Stroke, 35 Convent Dr., Bldg. 35, Rm. 2B-1012, Bethesda, MD 20892, USA
Lisi Wei
National Institute of Neurological Disorders and Stroke, 35 Convent Dr., Bldg. 35, Rm. 2B-1012, Bethesda, MD 20892, USA
Oleg Shupliakov
Department of Neuroscience, Karolinska Institutet, 17177 Stockholm, Sweden; Institute of Translational Biomedicine, St. Petersburg State University, 199034 St. Petersburg, Russia
Albert Jin
National Institute of Biomedical Imaging and Bioengineering (NIBIB), Bethesda, MD 20892, USA
Ben O’Shaughnessy
Department of Chemical Engineering, Columbia University, New York, NY 10027, USA; Corresponding author
Ling-Gang Wu
National Institute of Neurological Disorders and Stroke, 35 Convent Dr., Bldg. 35, Rm. 2B-1012, Bethesda, MD 20892, USA; Corresponding author
Summary: 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. : Shin et al. discover two fusion modes; one involves fused vesicle shrinking that employs a large pore to facilitate content release, and the other involves vesicle enlargement with a small pore that slows down release. Shrinking is energetically preferred over the generally assumed full-collapse fusion, because osmotic pressure squeezes fused vesicles. Keywords: exocytosis, transmitter release, hormone release, osmotic pressure, membrane dynamics, membrane fusion, vesicle shrinking, vesicle enlargement, bovine chromaffin cells, mathematical modeling, mathematical modeling
