Aminophospholipid translocase TAT-1 promotes phosphatidylserine exposure during C. elegans apoptosis.
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.
Züllig
Stephanie
S
Institute of Molecular Biology, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
Neukomm
Lukas J
LJ
Jovanovic
Marko
M
Charette
Steve J
SJ
Lyssenko
Nicholas N
NN
Halleck
Margaret S
MS
Reutelingsperger
Chris P M
CP
Schlegel
Robert A
RA
Hengartner
Michael O
MO
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015415:Biomarkers; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D047108:Embryonic Development / Q000235:genetics; D005854:Germ Cells / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000032:analysis; D030781:Organisms, Genetically Modified / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism*; D049294:Phospholipid Transfer Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D034622:RNA Interference
D015415:Biomarkers; D029742:Caenorhabditis elegans Proteins; D010718:Phosphatidylserines; D049294:Phospholipid Transfer Proteins; D049452:Green Fluorescent Proteins; C522446:TAT-1 protein, C elegans