Cytosolic phospholipase A2ε drives recycling through the clathrin-independent endocytic route

Mariagrazia Capestrano, Stefania Mariggio, Giuseppe Perinetti, Anastasia V. Egorova, Simona Iacobacci, Michele Santoro, Alessio Di Pentima, Cristiano Iurisci, Mikhail V. Egorov, Giuseppe Di Tullio, Roberto Buccione, Alberto Luini, Roman S. Polishchuk

Research output: Contribution to journalArticlepeer-review

Abstract

Previous studies have demonstrated that membrane tubulemediated transport events in biosynthetic and endocytic routes require phospholipase A2 (PLA2) activity. Here, we show that cytosolic phospholipase A2ε (cPLA2ε, also known as PLA2G4E) is targeted to the membrane compartments of the clathrinindependent endocytic route through a C-terminal stretch of positively charged amino acids, which allows the enzyme to interact with phosphoinositide lipids [especially PI(4,5)P2] that are enriched in clathrin-independent endosomes. Ablation of cPLA2ε suppressed the formation of tubular elements that carry internalized clathrin-independent cargoes, such as MHC-I, CD147 and CD55, back to the cell surface and, therefore, caused their intracellular retention. The ability of cPLA2ε to support recycling through tubule formation relies on the catalytic activity of the enzyme, because the inactive cPLA2εS420A mutant was not able to recover either tubule growth or transport from clathrin-independent endosomes. Taken together, our findings indicate that cPLA2ε is a new important regulator of trafficking processes within the clathrin-independent endocytic and recycling route. The affinity of cPLA2ε for this pathway supports a new hypothesis that different PLA2 enzymes use selective targeting mechanisms to regulate tubule formation locally during specific trafficking steps in the secretory and/or endocytic systems.

Original languageEnglish
Pages (from-to)977-993
Number of pages17
JournalJournal of Cell Science
Volume127
Issue number5
DOIs
Publication statusPublished - Mar 2014

Keywords

  • Clathrin-independent endocytosis
  • Membrane curvature
  • MHC-I trafficking
  • Phospholipas A2
  • Recycling tubules

ASJC Scopus subject areas

  • Cell Biology

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