Suzuki Jun-ichiro, Yamasaki Sho, Wu Jennifer, Koretzky Gary A, Saito Takashi
Department of Molecular Genetics, Graduate School of Medicine, Chiba University, Japan.
Blood. 2007 Jan 1;109(1):168-75. doi: 10.1182/blood-2005-12-020164. Epub 2006 Sep 14.
The dynamic rearrangement of the actin cytoskeleton plays critical roles in T-cell receptor (TCR) signaling and immunological synapse (IS) formation in T cells. Following actin rearrangement in T cells upon TCR stimulation, we found a unique ring-shaped reorganization of actin called the "actin cloud," which was specifically induced by outside-in signals through lymphocyte function-associated antigen-1 (LFA-1) engagement. In T-cell-antigen-presenting cell (APC) interactions, the actin cloud is generated in the absence of antigen and localized at the center of the T-cell-APC interface, where it accumulates LFA-1 and tyrosine-phosphorylated proteins. The LFA-1-induced actin cloud formation involves ADAP (adhesion- and degranulation-promoting adaptor protein) phosphorylation, LFA-1/ADAP assembly, and c-Jun N-terminal kinase (JNK) activation, and occurs independent of TCR and its proximal signaling. The formation of the actin cloud lowers the threshold for subsequent T-cell activation. Thus, the actin cloud induced by LFA-1 engagement may serve as a possible platform for LFA-1-mediated costimulatory function for T-cell activation.
肌动蛋白细胞骨架的动态重排在T细胞受体（TCR）信号传导以及T细胞免疫突触（IS）形成过程中发挥着关键作用。在TCR刺激后T细胞发生肌动蛋白重排后，我们发现了一种独特的肌动蛋白环形重排，称为“肌动蛋白云”，它是由通过淋巴细胞功能相关抗原-1（LFA-1）结合产生的由外向内信号特异性诱导的。在T细胞与抗原呈递细胞（APC）的相互作用中，肌动蛋白云在无抗原的情况下产生，并定位在T细胞-APC界面的中心，在那里它积累LFA-1和酪氨酸磷酸化蛋白。LFA-1诱导的肌动蛋白云形成涉及ADAP（促进黏附与脱颗粒的衔接蛋白）磷酸化、LFA-1/ADAP组装以及c-Jun氨基末端激酶（JNK）激活，并且独立于TCR及其近端信号传导发生。肌动蛋白云的形成降低了后续T细胞激活的阈值。因此，LFA-1结合诱导的肌动蛋白云可能作为LFA-1介导的T细胞激活共刺激功能的一个可能平台。
