Abstract
Transglutaminase 2 (TG2) is a protein crosslinking enzyme with many additional biological functions. We have previously shown that in TG2(-/-) mice the in vivo clearance of apoptotic cells is defective leading to autoimmunity. TG2 contributes to the formation of phagocytic portals by binding to both integrin beta(3), a known phagocytic receptor, and its bridging molecule, MFG-E8. In TG2 null macrophages integrin beta(3) cannot accumulate around the apoptotic cells and its signaling is impaired. In the present study we describe a subline of TG2 null mice, in which a compensatory increase in integrin beta(3) expression, which resulted alone in a high receptor concentration around the apoptotic cells without the requirement for accumulation, partially corrected the defect in integrin beta(3) signaling. Our data provide a proof for the concept that the function of TG2 is to stabilize accumulated integrin beta(3) concentration in the phagocytic cup.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis / immunology
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Cells, Cultured
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GTP Phosphohydrolases / metabolism
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GTP-Binding Proteins / genetics
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GTP-Binding Proteins / metabolism*
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Gene Expression
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Immunoblotting
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Integrin beta3 / genetics
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Integrin beta3 / metabolism*
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Macrophages, Peritoneal / cytology
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Macrophages, Peritoneal / immunology
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Macrophages, Peritoneal / metabolism*
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Mice
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Mice, Knockout
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Microscopy, Confocal
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Neuropeptides / metabolism
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Phagocytosis / immunology
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Phosphatidylinositols / metabolism
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Protein Glutamine gamma Glutamyltransferase 2
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Reverse Transcriptase Polymerase Chain Reaction
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Signal Transduction*
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Transglutaminases / genetics
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Transglutaminases / metabolism*
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rac GTP-Binding Proteins / metabolism
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rac1 GTP-Binding Protein
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rho GTP-Binding Proteins
Substances
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Integrin beta3
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Neuropeptides
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Phosphatidylinositols
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Rac1 protein, mouse
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Rhog protein, mouse
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Protein Glutamine gamma Glutamyltransferase 2
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Transglutaminases
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GTP Phosphohydrolases
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GTP-Binding Proteins
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rac GTP-Binding Proteins
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rac1 GTP-Binding Protein
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rho GTP-Binding Proteins