Curvature of clathrin-coated pits driven by epsin

Marijn G J Ford, Ian G Mills, Brian J Peter, Yvonne Vallis, Gerrit J K Praefcke, Philip R Evans, Harvey T McMahon

Research output: Contribution to journalArticlepeer-review

734 Citations (Scopus)

Abstract

Clathrin-mediated endocytosis involves cargo selection and membrane budding into vesicles with the aid of a protein coat. Formation of invaginated pits on the plasma membrane and subsequent budding of vesicles is an energetically demanding process that involves the cooperation of clathrin with many different proteins. Here we investigate the role of the brain-enriched protein epsin 1 in this process. Epsin is targeted to areas of endocytosis by binding the membrane lipid phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P(2)). We show here that epsin 1 directly modifies membrane curvature on binding to PtdIns(4,5)P(2) in conjunction with clathrin polymerization. We have discovered that formation of an amphipathic alpha-helix in epsin is coupled to PtdIns(4,5)P(2) binding. Mutation of residues on the hydrophobic region of this helix abolishes the ability to curve membranes. We propose that this helix is inserted into one leaflet of the lipid bilayer, inducing curvature. On lipid monolayers epsin alone is sufficient to facilitate the formation of clathrin-coated invaginations.

Original languageEnglish
Pages (from-to)361-6
Number of pages6
JournalNature
Volume419
Issue number6905
DOIs
Publication statusPublished - 26 Sep 2002

Keywords

  • Adaptor Proteins, Vesicular Transport
  • Amino Acid Sequence
  • Animals
  • Biopolymers
  • Brain
  • Carrier Proteins
  • Clathrin
  • Coated Pits, Cell-Membrane
  • Crystallography, X-Ray
  • Drosophila melanogaster
  • Endocytosis
  • Humans
  • Inositol 1,4,5-Trisphosphate
  • Liposomes
  • Membrane Proteins
  • Microscopy, Electron
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Neuropeptides
  • Phosphatidylinositol 4,5-Diphosphate
  • Protein Binding
  • Protein Structure, Tertiary
  • Rats
  • Vesicular Transport Proteins

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