1. Beyond the MUN domain, Munc13 controls priming and depriming of synaptic vesicles.
- Author
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Leitz J, Wang C, Esquivies L, Pfuetzner RA, Peters JJ, Couoh-Cardel S, Wang AL, and Brunger AT
- Subjects
- Animals, Mice, Protein Domains, Calcium metabolism, Membrane Fusion, Exocytosis, SNARE Proteins metabolism, Mice, Inbred C57BL, Neurons metabolism, Synaptic Vesicles metabolism, Nerve Tissue Proteins metabolism
- Abstract
Synaptic vesicle docking and priming are dynamic processes. At the molecular level, SNAREs (soluble NSF attachment protein receptors), synaptotagmins, and other factors are critical for Ca
2+ -triggered vesicle exocytosis, while disassembly factors, including NSF (N-ethylmaleimide-sensitive factor) and α-SNAP (soluble NSF attachment protein), disassemble and recycle SNAREs and antagonize fusion under some conditions. Here, we introduce a hybrid fusion assay that uses synaptic vesicles isolated from mouse brains and synthetic plasma membrane mimics. We included Munc18, Munc13, complexin, NSF, α-SNAP, and an ATP-regeneration system and maintained them continuously-as in the neuron-to investigate how these opposing processes yield fusogenic synaptic vesicles. In this setting, synaptic vesicle association is reversible, and the ATP-regeneration system produces the most synchronous Ca2+ -triggered fusion, suggesting that disassembly factors perform quality control at the early stages of synaptic vesicle association to establish a highly fusogenic state. We uncovered a functional role for Munc13 ancillary to the MUN domain that alleviates an α-SNAP-dependent inhibition of Ca2+ -triggered fusion., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)- Published
- 2024
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