A molecular mechanism for calcium-mediated synaptotagmin-triggered exocytosis
| Autor: | Volker Kiessling, Alex J. B. Kreutzberger, Binyong Liang, Sarah B. Nyenhuis, David S. Cafiso, J. David Castle, Lukas K. Tamm, Patrick Seelheim |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Models Molecular chemistry.chemical_element Calcium PC12 Cells Exocytosis Synaptotagmin 1 Article 03 medical and health sciences Synaptotagmins Protein Domains Structural Biology Animals Calcium Signaling Lipid bilayer Transport Vesicles Molecular Biology Calcium signaling Chemistry Qa-SNARE Proteins Lipid Metabolism Rats Transmembrane domain 030104 developmental biology Membrane Biophysics SNARE complex SNARE Proteins |
| Zdroj: | Nature structural & molecular biology |
| ISSN: | 1545-9985 |
| Popis: | The regulated exocytotic release of neurotransmitter and hormones is accomplished by a complex protein machinery whose core consists of SNARE proteins and the calcium sensor synaptotagmin-1. We propose a mechanism in which the lipid membrane is intimately involved in coupling calcium sensing to release. We found that fusion of dense core vesicles, derived from rat PC12 cells, was strongly linked to the angle between the cytoplasmic domain of the SNARE complex and the plane of the target membrane. We propose that, as this tilt angle increases, force is exerted on the SNARE transmembrane domains to drive the merger of the two bilayers. The tilt angle markedly increased following calcium-mediated binding of synaptotagmin to membranes, strongly depended on the surface electrostatics of the membrane, and was strictly coupled to the lipid order of the target membrane. |
| Databáze: | OpenAIRE |
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