Tóth Beáta, Garabuczi Eva, Sarang Zsolt, Vereb György, Vámosi György, Aeschlimann Daniel, Blaskó Bernadett, Bécsi Bálint, Erdõdi Ferenc, Lacy-Hulbert Adam, Zhang Ailiang, Falasca Laura, Birge Raymond B, Balajthy Zoltán, Melino Gerry, Fésüs László, Szondy Zsuzsa
Department of Biochemistry and Molecular Biology, Apoptosis and Genomics Research Group, Hungarian Academy of Sciences, Debrecen, Hungary.
J Immunol. 2009 Feb 15;182(4):2084-92. doi: 10.4049/jimmunol.0803444.
Transglutaminase 2 (TG2), a protein cross-linking enzyme with many additional biological functions, acts as coreceptor for integrin beta(3). We have previously shown that TG2(-/-) mice develop an age-dependent autoimmunity due to defective in vivo clearance of apoptotic cells. Here we report that TG2 on the cell surface and in guanine nucleotide-bound form promotes phagocytosis. Besides being a binding partner for integrin beta(3), a receptor known to mediate the uptake of apoptotic cells via activating Rac1, we also show that TG2 binds MFG-E8 (milk fat globulin EGF factor 8), a protein known to bridge integrin beta(3) to apoptotic cells. Finally, we report that in wild-type macrophages one or two engulfing portals are formed during phagocytosis of apoptotic cells that are characterized by accumulation of integrin beta(3) and Rac1. In the absence of TG2, integrin beta(3) cannot properly recognize the apoptotic cells, is not accumulated in the phagocytic cup, and its signaling is impaired. As a result, the formation of the engulfing portals, as well as the portals formed, is much less efficient. We propose that TG2 has a novel function to stabilize efficient phagocytic portals.
转谷氨酰胺酶2（TG2）是一种具有多种额外生物学功能的蛋白质交联酶，可作为整合素β3的共受体。我们之前已经表明，TG2基因敲除小鼠由于体内凋亡细胞清除缺陷而出现年龄依赖性自身免疫。在此我们报告，细胞表面以鸟嘌呤核苷酸结合形式存在的TG2可促进吞噬作用。除了作为整合素β3的结合伴侣外，整合素β3是一种已知通过激活Rac1介导凋亡细胞摄取的受体，我们还表明TG2可结合乳脂肪球表皮生长因子8（MFG-E8），一种已知可将整合素β3与凋亡细胞连接起来的蛋白质。最后，我们报告，在野生型巨噬细胞中，凋亡细胞吞噬过程中会形成一个或两个吞噬入口，其特征是整合素β3和Rac1的积累。在没有TG2的情况下，整合素β3无法正确识别凋亡细胞，不会在吞噬杯中积累，其信号传导也会受损。因此，吞噬入口的形成以及已形成的入口的效率要低得多。我们提出，TG2具有稳定高效吞噬入口的新功能。
