Phosphatidylinositol 4,5-bisphosphate clusters act as molecular beacons for vesicle recruitment.
Nat Struct Mol Biol
; 20(6): 679-86, 2013 Jun.
Article
em En
| MEDLINE
| ID: mdl-23665582
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Vesículas Sinápticas
/
Fosfatidilinositol 4,5-Difosfato
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Sinaptotagmina I
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Sintaxina 1
Limite:
Animals
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article