title: Calcium Promotes the Formation of Syntaxin 1 Mesoscale Domains through Phosphatidylinositol 4,5-Bisphosphate.
abstract: Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) is a minor component of total plasma membrane lipids, but it has a substantial role in the regulation of many cellular functions, including exo- and endocytosis. Recently, it was shown that PI(4,5)P2and syntaxin 1, a SNARE protein that catalyzes regulated exocytosis, form domains in the plasma membrane that constitute recognition sites for vesicle docking. Also, calcium was shown to promote syntaxin 1 clustering in the plasma membrane, but the molecular mechanism was unknown. Here, using a combination of superresolution stimulated emission depletion microscopy, FRET, and atomic force microscopy, we show that Ca(2+)acts as a charge bridge that specifically and reversibly connects multiple syntaxin 1/PI(4,5)P2complexes into larger mesoscale domains. This transient reorganization of the plasma membrane by physiological Ca(2+)concentrations is likely to be important for Ca(2+)-regulated secretion.
authors.affiliation: From the Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany, the Department of Neuroscience, Program in Cellular Neuroscience, Neurodegeneration, and Repair, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06511.
authors.forename: Dragomir
authors.identifier: http://orcid.org/0000-0002-6625-1879
authors.initials: D
authors.lastname: Milovanovic
authors.affiliation: the Third Institute of Physics, Faculty of Physics.
authors.forename: Mitja
authors.initials: M
authors.lastname: Platen
authors.affiliation: Institute for Organic and Biomolecular Chemistry, Georg August University, 37077 Göttingen, Germany.
authors.forename: Meike
authors.initials: M
authors.lastname: Junius
authors.affiliation: Institute for Organic and Biomolecular Chemistry, Georg August University, 37077 Göttingen, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Diederichsen
authors.affiliation: the Third Institute of Physics, Faculty of Physics, the School of Engineering and Physical Sciences, Heriot-Watt University, Edinburgh EH14 4AS, United Kingdom.
authors.forename: Iwan A T
authors.initials: IA
authors.lastname: Schaap
authors.affiliation: the Max Planck Institute for Molecular Cell Biology and Genetics, 01307 Dresden, Germany, and.
authors.forename: Alf
authors.initials: A
authors.lastname: Honigmann
authors.affiliation: From the Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany, rjahn@gwdg.de.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Jahn
authors.affiliation: From the Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany, the Department of Tumor Immunology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands geert.vandenbogaart@radboudumc.ru.nl.
authors.forename: Geert
authors.initials: G
authors.lastname: van den Bogaart
mesh_terms: D000818:Animals; D002118:Calcium / Q000737:chemistry / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D016716:PC12 Cells; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D051381:Rats; D050827:Syntaxin 1 / Q000378:metabolism*
chemical_list: D019269:Phosphatidylinositol 4,5-Diphosphate; D050827:Syntaxin 1; D002118:Calcium
keywords: PI(4,5)P2; SNARE proteins; calcium; clustering; membrane domains; membrane structure; plasma membrane; protein-lipid interaction; syntaxin 1