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PMID: 21316588 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Developmental cell ·Vol. 20 ·No. 2 ·2011-02-15 ·Pages 206-18

Chang-Ileto B, Frere SG, Chan RB, Voronov SV, Roux A, Di Paolo G

Abstract

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.

MeSH Terms
Adaptor Proteins, Signal Transducing/metabolism Animals Animals, Newborn COS Cells Cell Membrane/chemistry,metabolism Chlorocebus aethiops Dynamins/metabolism Hydrolysis Liposomes/metabolism Mice Nerve Tissue Proteins/chemistry,metabolism Phosphatidylinositol 4,5-Diphosphate/metabolism Phosphoric Monoester Hydrolases/chemistry,metabolism Phosphorylation Protein Binding Protein Structure, Tertiary Rats
Chemicals
Adaptor Proteins, Signal Transducing Liposomes Nerve Tissue Proteins Phosphatidylinositol 4,5-Diphosphate Sh3gl2 protein, mouse synaptojanin Phosphoric Monoester Hydrolases Dynamins
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Chang-Ileto Belle
Department of Pathology and Cell Biology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY 10032, USA.
Frere Samuel G
Chan Robin B
Voronov Sergey V
Roux Aurélien
Di Paolo Gilbert
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Article Info
Journal
Developmental cell
Abbr.
Dev Cell
ISSN
1878-1551
DOI
10.1016/j.devcel.2010.12.008
Published
2011-02-15
Pages
206-18
Language
English
Region
United States
NLM ID
101120028
PMCID
PMC3058127
Subset
IM
Grants
NINDS NIH HHS · R01 NS056049-02 · United States
NINDS NIH HHS · F31 NS058096-01A1 · United States
NINDS NIH HHS · F31 NS058096-02 · United States
NINDS NIH HHS · R01 NS056049-01 · United States
NINDS NIH HHS · F31 NS058096 · United States
NINDS NIH HHS · R01 NS056049-04 · United States
NINDS NIH HHS · F31 NS058096-03 · United States
NINDS NIH HHS · R01 NS056049-03 · United States
NINDS NIH HHS · R01 NS056049-05 · United States
NINDS NIH HHS · R01 NS056049 · United States
External Links
PubMed source DOI: 10.1016/j.devcel.2010.12.008 PMC Full Text View journal details
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