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Updated: Feb 21, 2026

Presynapse Formation Assay Using Presynapse Organizer Beads and “Neuron Ball” Culture
Published on: August 2, 2019
Hypothesis - buttressed rings assemble, clamp, and release SNAREpins for synaptic transmission
James E Rothman1, Shyam S Krishnakumar1, Kirill Grushin1
1Department of Cell Biology, Yale University School of Medicine, New Haven, CT, USA.
Abstract:
Neural networks are optimized to detect temporal coincidence on the millisecond timescale. Here, we offer a synthetic hypothesis based on recent structural insights into SNAREs and the C2 domain proteins to explain how synaptic transmission can keep this pace. We suggest that an outer ring of up to six curved Munc13 'MUN' domains transiently anchored to the plasma membrane via its flanking domains surrounds a stable inner ring comprised of synaptotagmin C2 domains to serve as a work-bench on which SNAREpins are templated. This 'buttressed-ring hypothesis' affords straightforward answers to many principal and long-standing questions concerning how SNAREpins can be assembled, clamped, and then released synchronously with an action potential.
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