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. © 2011 Elsevier Inc.
Chang-Ileto, B., Frere, S. G., Chan, R. B., Voronov, S. V., Roux, A., & Di Paolo, G. (2011). Synaptojanin 1-Mediated PI(4,5)P2 Hydrolysis Is Modulated by Membrane Curvature and Facilitates Membrane Fission. Developmental Cell, 20(2), 206–218. https://doi.org/10.1016/j.devcel.2010.12.008