Document Detail


Epidermal growth factor-like domain repeat of stabilin-2 recognizes phosphatidylserine during cell corpse clearance.
MedLine Citation:
PMID:  18573870     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Exposure of phosphatidylserine (PS) on the cell surface occurs early during apoptosis and serves as a recognition signal for phagocytes. Clearance of apoptotic cells by a membrane PS receptor is one of the critical anti-inflammatory functions of macrophages. However, the PS binding receptors and their recognition mechanisms have not been fully investigated. Recently, we reported that stabilin-2 is a PS receptor that mediates the clearance of apoptotic cells, thus releasing the anti-inflammatory cytokine, transforming growth factor beta. In this study, we showed that epidermal growth factor (EGF)-like domain repeats (EGFrp) in stabilin-2 can directly and specifically recognize PS. The EGFrps also competitively impaired apoptotic cell uptake by macrophages in in vivo models. We also showed that calcium ions are required for stabilin-2 to mediate phagocytosis via EGFrp. Interestingly, at least four tandem repeats of EGF-like domains were required to recognize PS, and the second atypical EGF-like domain in EGFrp was critical for calcium-dependent PS recognition. Considering that PS itself is an important target molecule for both apoptotic cells and nonapoptotic cells during various cellular processes, our results should help elucidate the molecular mechanism by which apoptotic cell clearance in the human body occurs and also have implications for targeting PS externalization of nonapoptotic cells.
Authors:
Seung-Yoon Park; So-Youn Kim; Mi-Yeon Jung; Dong-Jun Bae; In-San Kim
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-06-23
Journal Detail:
Title:  Molecular and cellular biology     Volume:  28     ISSN:  1098-5549     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-08-15     Completed Date:  2008-09-09     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5288-98     Citation Subset:  IM    
Affiliation:
Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Apoptosis / drug effects
Calcium / pharmacology
Cell Adhesion Molecules, Neuronal / chemistry*,  metabolism*
Cell Line
Erythrocytes / cytology,  drug effects,  metabolism
Humans
Macrophages / cytology,  drug effects,  metabolism
Mice
Molecular Sequence Data
Phagocytosis* / drug effects
Phosphatidylserines / metabolism*
Protein Structure, Tertiary
Repetitive Sequences, Amino Acid*
Sequence Alignment
Chemical
Reg. No./Substance:
0/Cell Adhesion Molecules, Neuronal; 0/Phosphatidylserines; 0/STAB2 protein, human; 7440-70-2/Calcium
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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