Membrane protein sequestering by ionic protein-lipid interactions |
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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 W Grubmüller Helmut Diederichsen Ulf Jahn Reinhard |
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Affiliation: | Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 G?ttingen, Germany. |
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Abstract: | Neuronal exocytosis is catalysed by the SNAP receptor protein syntaxin-1A, which is clustered in the plasma membrane at sites where synaptic vesicles undergo exocytosis. 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, co-reconstitution 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. |
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