Mehta Harshini, Glogauer Michael, Bécart Stephane, Altman Amnon, Coggeshall K Mark
Program in Immunobiology and Cancer, Oklahoma Medical Research Foundation, and Department of Cell Biology, University of Oklahoma, Oklahoma City, Oklahoma 73104, USA.
J Biol Chem. 2009 May 1;284(18):11882-91. doi: 10.1074/jbc.M809712200. Epub 2009 Feb 27.
SLAT (SWAP-70-like adaptor protein of T cells) is an adaptor protein expressed in cells of the hematopoietic system. SLAT interacts with and alters the function of small GTPase Rac1 in fibroblasts. In these nonhematopoietic models, the SLAT-Rac interaction leads to changes in F-actin and causes cytoskeletal reorganization. In T cells, SLAT expression regulates the development of T helper cells through Cdc42- and Rac1-mediated activation of the NF-AT transcription factor. Here we show that SLAT is expressed in macrophages. Overexpression of SLAT in a macrophage cell line inhibits the IgG Fcgamma receptor-mediated phagocytic ability of THP1 cells. In bone marrow-derived macrophages, SLAT protein is recruited to the early phagosomes formed via Fcgamma receptor engagement. SLAT recruitment to the phagosome was most efficient when the macrophages express at least one isoform of Rac (Rac1 or Rac2), because SLAT recruitment was reduced in macrophages of Rac-deficient mice. Macrophages derived from animals lacking SLAT show an elevation in the rate of Fcgamma receptor-mediated phagocytosis. The absence of SLAT is associated with an increase in the amount of F-actin formed around these phagosomes as well as an increase in the amount of Rac1 protein recruited to the phagosome. Our results suggest that SLAT acts as a gatekeeper for the amount of Rac recruited to the phagosomes formed by Fcgamma receptor engagement and thus is able to regulate F-actin re-organization and consequently phagocytosis.
SLAT（T细胞中类SWAP-70衔接蛋白）是一种在造血系统细胞中表达的衔接蛋白。SLAT在成纤维细胞中与小GTP酶Rac1相互作用并改变其功能。在这些非造血模型中，SLAT-Rac相互作用导致F-肌动蛋白发生变化并引起细胞骨架重组。在T细胞中，SLAT的表达通过Cdc42和Rac1介导的NF-AT转录因子激活来调节辅助性T细胞的发育。在此我们表明SLAT在巨噬细胞中表达。在巨噬细胞系中过表达SLAT会抑制THP1细胞的IgG Fcγ受体介导的吞噬能力。在骨髓来源的巨噬细胞中，SLAT蛋白被募集到通过Fcγ受体结合形成的早期吞噬体上。当巨噬细胞表达至少一种Rac同工型（Rac1或Rac2）时，SLAT募集到吞噬体的效率最高，因为在Rac缺陷小鼠的巨噬细胞中SLAT募集减少。缺乏SLAT的动物来源的巨噬细胞显示Fcγ受体介导的吞噬作用速率升高。SLAT的缺失与这些吞噬体周围形成的F-肌动蛋白量增加以及募集到吞噬体的Rac1蛋白量增加有关。我们的结果表明，SLAT作为Fcγ受体结合形成的吞噬体上募集的Rac量的守门人，因此能够调节F-肌动蛋白重组，进而调节吞噬作用。
