PI(4,5)P₂-binding effector proteins for vesicle exocytosis

Biochim Biophys Acta. 2015 Jun;1851(6):785-93. doi: 10.1016/j.bbalip.2014.09.017. Epub 2014 Oct 2.


PI(4,5)P₂participates directly in priming and possibly in fusion steps of Ca²⁺-triggered vesicle exocytosis. High concentration nanodomains of PI(4,5)P₂reside on the plasma membrane of neuroendocrine cells. A subset of vesicles that co-localize with PI(4,5)P₂ domains appear to undergo preferential exocytosis in stimulated cells. PI(4,5)P₂directly regulates vesicle exocytosis by recruiting and activating PI(4,5)P₂-binding proteins that regulate SNARE protein function including CAPS, Munc13-1/2, synaptotagmin-1, and other C2 domain-containing proteins. These PI(4,5)P₂effector proteins are coincidence detectors that engage in multiple interactions at vesicle exocytic sites. The SNARE protein syntaxin-1 also binds to PI(4,5)P₂, which promotes clustering, but an activating role for PI(4,5)P₂in syntaxin-1 function remains to be fully characterized. Similar principles underlie polarized constitutive vesicle fusion mediated in part by the PI(4,5)P₂-binding subunits of the exocyst complex (Sec3, Exo70). Overall, focal vesicle exocytosis occurs at sites landmarked by PI(4,5)P2, which serves to recruit and/or activate multifunctional PI(4,5)P₂-binding proteins. This article is part of a Special Issue entitled Phosphoinositides.

Keywords: CAPS/CADPS; Munc13; Phosphatidylinositol(4,5)bisphosphate; SNARE protein; Synaptotagmin; Vesicle exocytosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Biological Transport
  • Calcium / metabolism
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism
  • Exocytosis / genetics*
  • Gene Expression Regulation
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Phosphatidylinositol 4,5-Diphosphate / metabolism*
  • Protein Binding
  • Signal Transduction
  • Synaptotagmin I / genetics
  • Synaptotagmin I / metabolism
  • Syntaxin 1 / genetics
  • Syntaxin 1 / metabolism
  • Transport Vesicles / chemistry
  • Transport Vesicles / metabolism*
  • Vesicular Transport Proteins / genetics
  • Vesicular Transport Proteins / metabolism*


  • Calcium-Binding Proteins
  • Nerve Tissue Proteins
  • Phosphatidylinositol 4,5-Diphosphate
  • Synaptotagmin I
  • Syntaxin 1
  • Vesicular Transport Proteins
  • Calcium