A lever hypothesis for Synaptotagmin-1 action in neurotransmitter release
成果类型：
Article
署名作者：
Jaczynska, Klaudia; Esser, Victoria; Xu, Junjie; Sari, Levent; Lin, Milo M.; Rosenmund, Christian; Rizo, Josep
署名单位：
University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; Free University of Berlin; Humboldt University of Berlin
刊物名称：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN/ISSBN：
0027-10172
DOI：
10.1073/pnas.2417941121
发表日期：
2025-01-07
关键词：
3-dimensional structure
snare complex
phospholipid-binding
membrane-fusion
ca2+ binding
domain
munc13
exocytosis
regulator
machinery
摘要：
Neurotransmitter release is triggered in microseconds by Ca2+- binding to the dles between synaptic vesicles and plasma membranes, but the coupling mechanism between Ca2+- sensing and membrane fusion is unknown. Release requires extension of SNARE helices into juxtamembrane linkers that precede transmembrane regions (linker through a primary interface comprising two regions (I and II). The Synaptotagmin- 1 curvature, perturbing lipid bilayers, or helping bridge the membranes, but SNARE from the fusion site, hindering these putative activities. To clarify this paradox, we have used NMR and fluorescence spectroscopy. NMR experiments reveal that binding of C2B domain arginines to SNARE acidic residues at region II remains after disruption of region I, and that a mutation that impairs spontaneous and Ca2+- triggered neurotransSNARE complex but causes reorientation of the C2B domain. Based on these results domain reorients on the membrane and dissociates from the SNAREs at region I but linker zippering or other SNARE structural changes required for fast membrane fusion.