Over-expression of integrin beta3 can partially overcome the defect of integrin beta3 signaling in transglutaminase 2 null macrophages.
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.
Tóth
Beáta
B
Department of Biochemistry and Molecular Biology, Apoptosis and Genomics Research Group, Hungarian Academy of Sciences, University of Debrecen, Nagyerdei krt. 98, Debrecen H-4012, Hungary.
Sarang
Zsolt
Z
Vereb
György
G
Zhang
Ailiang
A
Tanaka
Sakae
S
Melino
Gerry
G
Fésüs
László
L
Szondy
Zsuzsa
Z
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D002478:Cells, Cultured; D020558:GTP Phosphohydrolases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D015151:Immunoblotting; D039661:Integrin beta3 / Q000235:genetics / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D009479:Neuropeptides / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology; D010716:Phosphatidylinositols / Q000378:metabolism; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D011503:Transglutaminases / Q000235:genetics / Q000378:metabolism*; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins
D039661:Integrin beta3; D009479:Neuropeptides; D010716:Phosphatidylinositols; C484602:Rac1 protein, mouse; C489577:Rhog protein, mouse; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins