Document Detail

CED-1, CED-7, and TTR-52 regulate surface phosphatidylserine expression on apoptotic and phagocytic cells.
MedLine Citation:
PMID:  22727702     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Phosphatidylserine (PS) normally confined to the cytoplasmic leaflet of plasma membrane (PM) is externalized to the exoplasmic leaflet (exPS) during apoptosis, where it serves as an "eat-me" signal to phagocytes. In addition, some living cells such as macrophages also express exPS.
RESULTS: A secreted Annexin V (sAnxV::GFP) PS sensor reveals that exPS appears early on apoptotic cells in C. elegans embryos and decreases in older or unengulfed apoptotic cells. This decrease in exPS expression is blocked by loss of CED-7, an ATP binding cassette (ABC) transporter, or TTR-52, a secreted PS binding protein. Phagocytic cells also express exPS, which is dependent on the activity of CED-7, TTR-52, and TTR-52-interacting phagocyte receptor CED-1. Interestingly, a secreted lactadherin PS sensor (sGFP::Lact(C1C2)) labels apoptotic cells but not phagocytes, prevents sAnxV::GFP from labeling phagocytes, and compromises phagocytosis. Immuno-electron micrographs of embryos expressing sAnxV::GFP or sGFP::Lact(C1C2) reveal the presence of extracellular PS-containing vesicles between the apoptotic cell and neighboring cells, which are absent or greatly reduced in the ced-7 and ttr-52 mutants, respectively, indicating that CED-7 and TTR-52 promote the generation of extracellular PS vesicles. Loss of the tat-1 gene, which maintains PS asymmetry in the PM, restores phagocyte exPS expression in ced-1, ced-7, and ttr-52 mutants and partially rescues their engulfment defects.
CONCLUSIONS: CED-7 and TTR-52 may promote the efflux of PS from apoptotic cells through the generation of extracellular PS vesicles, which lead to exPS expression on phagocytes via TTR-52 and CED-1 to facilitate cell corpse clearance.
James Mapes; Yu-Zen Chen; Anna Kim; Shohei Mitani; Byung-Ho Kang; Ding Xue
Publication Detail:
Type:  Evaluation Studies; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-06-21
Journal Detail:
Title:  Current biology : CB     Volume:  22     ISSN:  1879-0445     ISO Abbreviation:  Curr. Biol.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-07-27     Completed Date:  2012-11-30     Revised Date:  2013-11-06    
Medline Journal Info:
Nlm Unique ID:  9107782     Medline TA:  Curr Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1267-75     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Ltd. All rights reserved.
Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
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MeSH Terms
ATP-Binding Cassette Transporters / genetics,  metabolism*
Annexin A5 / metabolism
Caenorhabditis elegans / genetics,  metabolism*
Caenorhabditis elegans Proteins / genetics,  metabolism*
Carrier Proteins / genetics,  metabolism*
Embryo, Nonmammalian / metabolism
Membrane Proteins / genetics,  metabolism*
Microscopy, Immunoelectron / methods*
Phagocytes / metabolism
Phosphatidylserines / metabolism*
Grant Support
Reg. No./Substance:
0/Annexin A5; 0/CED-7 protein, C elegans; 0/Caenorhabditis elegans Proteins; 0/Carrier Proteins; 0/Membrane Proteins; 0/Phosphatidylserines; 0/TTR-52 protein, C elegans; 0/ced-1 protein, C elegans

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