C2 domain membrane penetration by group IVA cytosolic phospholipase A 2 induces membrane curvature changes

Katherine E. Ward, James P. Ropa, Emmanuel Adu-Gyamfi, Robert V. Stahelin

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Group IVA cytosolic phospholipase A2 (cPLA2α) is an 85 kDa enzyme that regulates the release of arachidonic acid (AA) from the sn-2 position of membrane phospholipids. It is well established that cPLA 2α binds zwitterionic lipids such as phosphatidylcholine in a Ca2+-dependent manner through its N-terminal C2 domain, which regulates its translocation to cellular membranes. In addition to its role in AA synthesis, it has been shown that cPLA2α promotes tubulation and vesiculation of the Golgi and regulates traffi cking of endosomes. Additionally, the isolated C2 domain of cPLA2α is able to reconstitute Fc receptor-mediated phagocytosis, suggesting that C2 domain membrane binding is sufficient for phagosome formation. These reported activities of cPLA2α and its C2 domain require changes in membrane structure, but the ability of the C2 domain to promote changes in membrane shape has not been reported. Here we demonstrate that the C2 domain of cPLA2α is able to induce membrane curvature changes to lipid vesicles, giant unilamellar vesicles, and membrane sheets. Biophysical assays combined with mutagenesis of C2 domain residues involved in membrane penetration demonstrate that membrane insertion by the C2 domain is required for membrane deformation, suggesting that C2 domain-induced membrane structural changes may be an important step in signaling pathways mediated by cPLA2α.

Original languageEnglish (US)
Pages (from-to)2656-2666
Number of pages11
JournalJournal of Lipid Research
Volume53
Issue number12
DOIs
StatePublished - Dec 1 2012

Keywords

  • Calcium
  • Cytosolic phospholipase Aα
  • Lipid binding

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Endocrinology

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