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

Phosphatidylinositol 4,5-bisphosphate clusters act as molecular beacons for vesicle recruitment.
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DOI:
10.1038/nsmb.2570
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发表时间:
2013-06
影响因子:
16.8
通讯作者:
Jahn, Reinhard
Jahn, Reinhard
中科院分区:
生物学1区
文献类型:
--
作者:
Honigmann, Alf;van den Bogaart, Geert;Iraheta, Emilio;Risselada, H. Jelger;Milovanovic, Dragomir;Mueller, Veronika;Muellar, Stefan;Diederichsen, Ulf;Fasshauer, Dirk;Grubmueller, Helmut;Hell, Stefan W.;Eggeling, Christian;Kuehnel, Karin;Jahn, Reinhard

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Synaptic vesicle exocytosis is mediated by the vesicular Ca2+-sensor synaptotagmin-1. Synaptotagmin-1 interacts with the SNARE protein syntaxin-1A and with acidic phospholipids such as phosphatidylinositol 4,5-bisphosphate (PIP2). However, it is unclear how these interactions contribute to triggering membrane fusion. Using both PC12 cells from Rattus norvegicus and artificial supported bilayers we now show that synaptotagmin-1 interacts with the polybasic linker region of syntaxin-1A independent of Ca2+ via PIP2. This interaction allows both Ca2+-binding sites of synaptotagmin-1 to bind to phosphatidylserine (PS) in the vesicle membrane upon Ca2+-triggering. We determined the crystal structure of the C2B-domain of synaptotagmin-1 bound to phosphoserine, allowing for developing 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 Ca2+-influx bringing the vesicle membrane close enough for membrane fusion.
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