A molecular mechanism for calcium-mediated synaptotagmin-triggered exocytosis.

Abstract:

: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.

journal_name

Nat Struct Mol Biol

authors

Kiessling V,Kreutzberger AJB,Liang B,Nyenhuis SB,Seelheim P,Castle JD,Cafiso DS,Tamm LK

doi

10.1038/s41594-018-0130-9

subject

Has Abstract

pub_date

2018-10-01 00:00:00

pages

911-917

issue

10

eissn

1545-9993

issn

1545-9985

pii

10.1038/s41594-018-0130-9

journal_volume

25

pub_type

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