Calcium Promotes the Formation of Syntaxin 1 Mesoscale Domains through Phosphatidylinositol 4,5-Bisphosphate

Dragomir Milovanovic, Mitja Platen, Meike Junius, Ulf Diederichsen, Iwan Schaap, Alf Honigmann, Reinhard Jahn, Geert van den Bogaart

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Abstract

Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P-2) 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)P-2 and 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 Ca2+ acts as a charge bridge that specifically and reversibly connects multiple syntaxin 1/PI(4,5)P-2 complexes into larger mesoscale domains. This transient reorganization of the plasma membrane by physiological Ca2+ concentrations is likely to be important for Ca2+-regulated secretion.

Original languageEnglish
Pages (from-to)7868-7876
Number of pages9
JournalJournal of Biological Chemistry
Volume291
Issue number15
Early online date16 Feb 2016
DOIs
Publication statusPublished - 8 Apr 2016

Keywords

  • calcium
  • membrane structure
  • plasma membrane
  • protein-lipid interaction
  • SNARE proteins
  • PI(4
  • 5)P-2
  • clustering
  • membrane domains
  • syntaxin 1
  • PLASMA-MEMBRANE
  • NEUROTRANSMITTER RELEASE
  • SECRETORY GRANULES
  • SYNAPTIC VESICLE
  • FORCE MICROSCOPY
  • T-SNARE
  • CLUSTERS
  • EXOCYTOSIS
  • MICRODOMAINS
  • SITES

Cite this

Milovanovic, D., Platen, M., Junius, M., Diederichsen, U., Schaap, I., Honigmann, A., Jahn, R., & van den Bogaart, G. (2016). Calcium Promotes the Formation of Syntaxin 1 Mesoscale Domains through Phosphatidylinositol 4,5-Bisphosphate. Journal of Biological Chemistry, 291(15), 7868-7876. https://doi.org/10.1074/jbc.M116.716225