Phosphatidylinositol 4,5-bisphosphate clusters act as molecular beacons for vesicle recruitment
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
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.
Details
Original language | English |
---|---|
Pages (from-to) | 679-686 |
Number of pages | 8 |
Journal | Nature Structural and Molecular Biology |
Volume | 20 |
Issue number | 6 |
Publication status | Published - Jun 2013 |
Peer-reviewed | Yes |
Externally published | Yes |
External IDs
PubMed | 23665582 |
---|---|
ORCID | /0000-0003-0475-3790/work/161889561 |