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CD31 delays phagocyte membrane repolarization to promote efficient binding of apoptotic cells
Author(s) -
VerWilson Elizabeth F.,
Auradé Frédéric,
Tian Lijun,
Rowe Iain C. M.,
Shipston Michael J.,
Savill John,
Brown Simon B.
Publication year - 2007
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0507283
Subject(s) - microbiology and biotechnology , biology , phagocytosis , integrin , receptor , biochemistry
Homophilic ligation of CD31, a member of the Ig superfamily of adhesion receptors, promotes macrophage clearance of apoptotic leukocytes by a mechanism hitherto not described. In studying CD31‐dependent regulation of β1‐integrin binding of fibronectin‐coated Latex™ beads, we discovered a role for the voltage‐gated potassium channel ether‐à‐go‐go ‐related gene (ERG) as a downstream effector of CD31 signaling. ERG was identified by tandem mass spectrometry as a 140‐kDa protein, which was selectively modified with biotin following the targeted delivery of a biotin‐transfer reagent to CD31 using Fab fragments of an anti‐CD31 mAb. Similar results were obtained with macrophages but not K562 cells, expressing a truncated cytoplasmic tail of CD31, which failed to regulate bead binding. Colocalization of CD31 with ERG was confirmed by immunofluorescence for K562 cells and macrophages. We now demonstrate that the resting membrane potential of macrophages is depolarized on contact with apoptotic cells and that CD31 inhibits the ERG current, which would otherwise function to repolarize. Sustained depolarization favored the firm binding of phagocytic targets, a prerequisite for efficient engulfment. Our results identify ERG as a downstream effector of CD31 in the regulation of integrin‐dependent binding of apoptotic cells by macrophages.