Phosphatidylinositol 4,5-bisphosphate clusters act as molecular beacons for vesicle recruitment.

Details

Serval ID
serval:BIB_2132D45084C0
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Phosphatidylinositol 4,5-bisphosphate clusters act as molecular beacons for vesicle recruitment.
Journal
Nature Structural and Molecular Biology
Author(s)
Honigmann A., van den Bogaart G., Iraheta E., Risselada H.J., Milovanovic D., Mueller V., Müllar S., Diederichsen U., Fasshauer D., Grubmüller H., Hell S.W., Eggeling C., Kühnel K., Jahn R.
ISSN
1545-9985 (Electronic)
ISSN-L
1545-9985
Publication state
Published
Issued date
2013
Peer-reviewed
Oui
Volume
20
Number
6
Pages
679-686
Language
english
Abstract
Synaptic-vesicle exocytosis is mediated by the vesicular Ca(2+) sensor synaptotagmin-1. Synaptotagmin-1 interacts with the SNARE protein syntaxin-1A and acidic phospholipids such as phosphatidylinositol 4,5-bisphosphate (PIP2). However, it is unclear how these interactions contribute to triggering membrane fusion. Using PC12 cells from Rattus norvegicus and artificial supported bilayers, we show that synaptotagmin-1 interacts with the polybasic linker region of syntaxin-1A independent of Ca(2+) through PIP2. This interaction allows both Ca(2+)-binding sites of synaptotagmin-1 to bind to phosphatidylserine in the vesicle membrane upon Ca(2+) triggering. We determined the crystal structure of the C2B domain of synaptotagmin-1 bound to phosphoserine, allowing development of a high-resolution model of synaptotagmin bridging two different membranes. Our results suggest that PIP2 clusters organized by syntaxin-1 act as molecular beacons for vesicle docking, with the subsequent Ca(2+) influx bringing the vesicle membrane close enough for membrane fusion.
Pubmed
Web of science
Create date
23/07/2013 13:27
Last modification date
20/08/2019 12:57
Usage data