Phosphatidylserine exposure during apoptosis reflects bidirectional trafficking between plasma membrane and cytoplasm

S. H. Lee, X. W. Meng, K. S. Flatten, D. A. Loegering, S. H. Kaufmann

Research output: Contribution to journalArticlepeer-review

106 Scopus citations

Abstract

Phosphatidylserine (PS) exposure on the external leaflet of the plasma membrane is widely observed during apoptosis and forms the basis for the annexin V binding assay to detect apoptotic cell death. Current efforts to explain PS exposure focus on two potential mechanisms, activation of a phospholipid scramblase or calcium-mediated trafficking of lysosomes to the cell surface. Here, we provide evidence that apoptotic PS exposure instead reflects bidirectional trafficking of membrane between the cell surface and cytoplasm. Using a series of cell lines, some of which expose large amounts of PS during apoptosis and some of which do not, we demonstrate that accumulation of plasma membrane-derived cytoplasmic vesicles in a dynamin-, clathrin-and Cdc42-independent manner is a previously undescribed but widely occurring feature of apoptosis. The apoptotic exposure of PS occurs when these vesicles traffic back to cell surface in a calcium-dependent process that is deficient in a substantial fraction of human cancer cell lines. These observations provide a new model for PS externalization during apoptosis and simultaneously identify an altered step that accounts for the paucity of apoptotic PS exposure in many cell lines.

Original languageEnglish (US)
Pages (from-to)64-76
Number of pages13
JournalCell Death and Differentiation
Volume20
Issue number1
DOIs
StatePublished - Jan 2013

Keywords

  • Annexin V
  • membrane vesicles
  • phosphatidylserine

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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