Synaptojanin 1-mediated PI(4,5)P2 hydrolysis is modulated by membrane curvature and facilitates membrane fission

Dev Cell. 2011 Feb 15;20(2):206-18. doi: 10.1016/j.devcel.2010.12.008.


Phosphatidylinositol-4,5-bisphosphate [PI(4,5)P₂] plays a fundamental role in clathrin-mediated endocytosis. However, precisely how PI(4,5)P₂ metabolism is spatially and temporally regulated during membrane internalization and the functional consequences of endocytosis-coupled PI(4,5)P₂ dephosphorylation remain to be explored. Using cell-free assays with liposomes of varying diameters, we show that the major synaptic phosphoinositide phosphatase, synaptojanin 1 (Synj1), acts with membrane curvature generators/sensors, such as the BAR protein endophilin, to preferentially remove PI(4,5)P₂ from curved membranes as opposed to relatively flat ones. Moreover, in vivo recruitment of Synj1's inositol 5-phosphatase domain to endophilin-induced membrane tubules results in fragmentation and condensation of these structures largely in a dynamin-dependent fashion. Our study raises the possibility that geometry-based mechanisms may contribute to spatially restricting PI(4,5)P₂ elimination during membrane internalization and suggests that the PI(4,5)P₂-to-PI4P conversion achieved by Synj1 at sites of high curvature may cooperate with dynamin to achieve membrane fission.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Animals, Newborn
  • COS Cells
  • Cell Membrane / chemistry*
  • Cell Membrane / metabolism*
  • Chlorocebus aethiops
  • Dynamins / metabolism
  • Hydrolysis
  • Liposomes / metabolism
  • Mice
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / metabolism*
  • Phosphatidylinositol 4,5-Diphosphate / metabolism*
  • Phosphoric Monoester Hydrolases / chemistry
  • Phosphoric Monoester Hydrolases / metabolism*
  • Phosphorylation
  • Protein Binding
  • Protein Structure, Tertiary
  • Rats


  • Adaptor Proteins, Signal Transducing
  • Liposomes
  • Nerve Tissue Proteins
  • Phosphatidylinositol 4,5-Diphosphate
  • Sh3gl2 protein, mouse
  • synaptojanin
  • Phosphoric Monoester Hydrolases
  • Dynamins