Aminophospholipid translocase TAT-1 promotes phosphatidylserine exposure during C. elegans apoptosis

Curr Biol. 2007 Jun 5;17(11):994-9. doi: 10.1016/j.cub.2007.05.024.

Abstract

Phospholipids are distributed asymmetrically across the plasma-membrane bilayer of eukaryotic cells: Phosphatidylserine (PS), phosphatidylethanolamine, and phosphoinositides are predominantly restricted to the inner leaflet, whereas phophatidylcholine and sphingolipids are enriched on the outer leaflet [1, 2]. Exposure of PS on the cell surface is a conserved feature of apoptosis and plays an important role in promoting the clearance of apoptotic cells by phagocytosis [3]. However, the molecular mechanism that drives PS exposure remains mysterious. To address this issue, we studied cell-surface changes during apoptosis in the nematode C. elegans. Here, we show that PS exposure can readily be detected on apoptotic C. elegans cells. We generated a transgenic strain expressing a GFP::Annexin V reporter to screen for genes required for this process. Although none of the known engulfment genes was required, RNAi knockdown of the putative aminophospholipid transporter gene tat-1 abrogated PS exposure on apoptotic cells. tat-1(RNAi) also reduced the efficiency of cell-corpse clearance, suggesting that PS exposure acts as an "eat-me" signal in worms. We propose that tat-1 homologs might also play an important role in PS exposure in mammals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Biomarkers
  • Caenorhabditis elegans / cytology*
  • Caenorhabditis elegans / enzymology
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / antagonists & inhibitors
  • Caenorhabditis elegans Proteins / metabolism
  • Caenorhabditis elegans Proteins / physiology*
  • Cell Membrane / metabolism*
  • Cells, Cultured
  • Embryonic Development / genetics
  • Germ Cells / metabolism
  • Green Fluorescent Proteins / analysis
  • Organisms, Genetically Modified / metabolism
  • Phosphatidylserines / metabolism*
  • Phospholipid Transfer Proteins / antagonists & inhibitors
  • Phospholipid Transfer Proteins / metabolism
  • Phospholipid Transfer Proteins / physiology*
  • RNA Interference

Substances

  • Biomarkers
  • Caenorhabditis elegans Proteins
  • Phosphatidylserines
  • Phospholipid Transfer Proteins
  • Green Fluorescent Proteins
  • TAT-1 protein, C elegans