Abstract:
:Synaptic vesicles fuse with the plasma membrane in response to Ca(2+) influx, thereby releasing neurotransmitters into the synaptic cleft. The protein machinery that mediates this process, consisting of soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) and regulatory proteins, is well known, but the mechanisms by which these proteins prime synaptic membranes for fusion are debated. In this study, we applied large-scale, automated cryo-electron tomography to image an in vitro system that reconstitutes synaptic fusion. Our findings suggest that upon docking and priming of vesicles for fast Ca(2)(+)-triggered fusion, SNARE proteins act in concert with regulatory proteins to induce a local protrusion in the plasma membrane, directed towards the primed vesicle. The SNAREs and regulatory proteins thereby stabilize the membrane in a high-energy state from which the activation energy for fusion is profoundly reduced, allowing synchronous and instantaneous fusion upon release of the complexin clamp.
journal_name
EMBO Repjournal_title
EMBO reportsauthors
Bharat TA,Malsam J,Hagen WJ,Scheutzow A,Söllner TH,Briggs JAdoi
10.1002/embr.201337807subject
Has Abstractpub_date
2014-03-01 00:00:00pages
308-14issue
3eissn
1469-221Xissn
1469-3178pii
embr.201337807journal_volume
15pub_type
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