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Hypothesis – buttressed rings assemble, clamp, and release SNAREpins for synaptic transmission
Author(s) -
Rothman James E.,
Krishnakumar Shyam S.,
Grushin Kirill,
Pincet Frederic
Publication year - 2017
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12874
Subject(s) - synaptotagmin 1 , c2 domain , neurotransmission , biophysics , ring (chemistry) , chemistry , neuroscience , synaptic vesicle , biology , membrane , vesicle , receptor , biochemistry , organic chemistry
Neural networks are optimized to detect temporal coincidence on the millisecond timescale. Here, we offer a synthetic hypothesis based on recent structural insights into SNARE s 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 SNARE pins are templated. This ‘buttressed‐ring hypothesis’ affords straightforward answers to many principal and long‐standing questions concerning how SNARE pins can be assembled, clamped, and then released synchronously with an action potential.