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Symmetrical organization of proteins under docked synaptic vesicles
Author(s) -
Li Xia,
Radhakrishnan Abhijith,
Grushin Kirill,
Kasula Ravikiran,
Chaudhuri Arunima,
Gomathinayagam Sujatha,
Krishnakumar Shyam S.,
Liu Jun,
Rothman James E.
Publication year - 2019
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 - 10.1002/1873-3468.13316
Subject(s) - synaptotagmin 1 , exocytosis , synaptic vesicle , vesicle , vesicle fusion , stx1a , munc 18 , microbiology and biotechnology , chemistry , snare complex , calcium , biophysics , biology , biochemistry , membrane , organic chemistry
During calcium‐regulated exocytosis, the constitutive fusion machinery is ‘clamped’ in a partially assembled state until synchronously released by calcium. The protein machinery involved in this process is known, but the supra ‐molecular architecture and underlying mechanisms are unclear. Here, we use cryo‐electron tomography analysis in nerve growth factor‐differentiated neuro‐endocrine (PC12) cells to delineate the organization of the release machinery under the docked vesicles. We find that exactly six exocytosis modules, each likely consisting of a single SNARE pin with its bound Synaptotagmins, Complexin, and Munc18 proteins, are symmetrically arranged at the vesicle–PM interface. Mutational analysis suggests that the symmetrical organization is templated by circular oligomers of Synaptotagmin. The observed arrangement, including its precise radial positioning, is in‐line with the recently proposed ‘buttressed ring hypothesis’.