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Updated: Jul 3, 2026

Measuring Synaptic Vesicle Endocytosis in Cultured Hippocampal Neurons
Published on: September 4, 2017
Turbocharging synaptic transmission: 12 SNAREpins are required for rapid release of reconstituted synaptic vesicles
Manindra Bera1,2, Atrouli Chatterjee1,2, Amit Koikkarah Aji1,2
1Department of Cell Biology, Yale School of Medicine, New Haven, CT 06520, USA.
Abstract:
Synaptic transmission occurs synchronously with real-world events, far faster than vesicle fusion for hormone release or membrane biogenesis, all mediated by soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complexes. How SNAREs cooperate to achieve synchronous neurotransmitter release is a long-standing mystery. Rapid release (<7 milliseconds) has been reconstituted from purified synaptic SNAREs, SNARE-assembling chaperones, and calcium ion sensors in a fully-defined, genetically validated system that enables single-molecule counting in docked vesicles before release. SNAREpin complexes (12 ± 0.3) are found in each such ready-release vesicle, suggesting a regular structure. Several genetic conditions (including point mutation of the synaptic vesicle protein Synaptophysin from a Synaptopathy patient and human and mouse disease mutations of the synaptic vesicle protein vesicle-associated membrane protein-2 (VAMP2) reduce the number of SNAREpins to 6 ± 0.3 and result in profoundly delayed release over 0.1 to 1 seconds. Omitting Synaptophysin, whose hexamers preassemble 12 copies of VAMP2, also yields ~6 SNAREpins and delays release.
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