Abstract
AbstractCompensatory endocytosis keeps the membrane surface area of secretory cells constant following exocytosis. At chemical synapses, clathrin-independent ultrafast endocytosis maintains such homeostasis. This endocytic pathway is temporally and spatially coupled to exocytosis; it initiates within 50 ms at the region immediately next to the active zone where vesicles fuse. However, the coupling mechanism is unknown. Here, we demonstrate that filamentous actin is organized as a ring, surrounding the active zone at mouse hippocampal synapses. Assuming the membrane area conservation is due to this actin ring, our theoretical model suggests that flattening of fused vesicles exerts lateral compression in the plasma membrane, resulting in rapid formation of endocytic pits at the border between the active zone and the surrounding actin-enriched region. Consistent with model predictions, our data show that ultrafast endocytosis requires sufficient compression by exocytosis of multiple vesicles and does not initiate when actin organization is disrupted, either pharmacologically or by ablation of the actin-binding protein Epsin1. Our work suggests that membrane mechanics underlie the rapid coupling of exocytosis to endocytosis at synapses.
Funder
U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke
National Science Foundation
McKnight Endowment Fund for Neuroscience
Esther A. and Joseph Klingenstein Fund
Vallee Foundation
Alfred P. Sloan Foundation
U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences
Japan Society for the Promotion of Science London
U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse
Howard Hughes Medical Institute
U.S. Department of Health & Human Services | NIH | National Institute of Mental Health
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
Cited by
5 articles.
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