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

J Biol Chem. 2016 Apr 8;291(15):7868-76. doi: 10.1074/jbc.M116.716225. Epub 2016 Feb 16.


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.

Keywords: PI(4,5)P2; SNARE proteins; calcium; clustering; membrane domains; membrane structure; plasma membrane; protein-lipid interaction; syntaxin 1.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / chemistry
  • Calcium / metabolism*
  • Cell Membrane / metabolism*
  • PC12 Cells
  • Phosphatidylinositol 4,5-Diphosphate / metabolism*
  • Protein Structure, Tertiary
  • Rats
  • Syntaxin 1 / metabolism*


  • Phosphatidylinositol 4,5-Diphosphate
  • Syntaxin 1
  • Calcium