Membrane protein sequestering by ionic protein-lipid interactions
2011 | journal article; research paper. A publication with affiliation to the University of Göttingen.
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- Authors
- van den Bogaart, Geert; Meyenberg, Karsten; Risselada, H. Jelger ; Amin, Hayder; Willig, Katrin I. ; Hubrich, Barbara E.; Dier, Markus; Hell, Stefan ; Grubmüller, Helmut ; Diederichsen, Ulf ; Jahn, Reinhard
- Abstract
- Neuronal exocytosis is catalysed by the SNAP receptor protein syntaxin-1A(1), which is clustered in the plasma membrane at sites where synaptic vesicles undergo exocytosis(2,3). However, how syntaxin-1A is sequestered is unknown. Here we show that syntaxin clustering is mediated by electrostatic interactions with the strongly anionic lipid phosphatidylinositol-4,5-bisphosphate (PIP2). Using super-resolution stimulated-emission depletion microscopy on the plasma membranes of PC12 cells, we found that PIP2 is the dominant inner-leaflet lipid in microdomains about 73 nanometres in size. This high accumulation of PIP2 was required for syntaxin-1A sequestering, as destruction of PIP2 by the phosphatase synaptojanin-1 reduced syntaxin-1A clustering. Furthermore, coreconstitution of PIP2 and the carboxy-terminal part of syntaxin-1A in artificial giant unilamellar vesicles resulted in segregation of PIP2 and syntaxin-1A into distinct domains even when cholesterol was absent. Our results demonstrate that electrostatic protein-lipid interactions can result in the formation of microdomains independently of cholesterol or lipid phases.
- Issue Date
- 2011
- Journal
- Nature
- ISSN
- 0028-0836
- Language
- English