Vukcevic Mirko, Spagnoli Giulio C, Iezzi Giandomenica, Zorzato Francesco, Treves Susan
Department of Anaesthesia, Basel University Hospital, 4031 Basel, Switzerland.
J Biol Chem. 2008 Dec 12;283(50):34913-22. doi: 10.1074/jbc.M804472200. Epub 2008 Oct 16.
Dendritic cells express the skeletal muscle ryanodine receptor (RyR1), yet little is known concerning its physiological role and activation mechanism. Here we show that dendritic cells also express the Ca(v)1.2 subunit of the L-type Ca(2+) channel and that release of intracellular Ca(2+) via RyR1 depends on the presence of extracellular Ca(2+) and is sensitive to ryanodine and nifedipine. Interestingly, RyR1 activation causes a very rapid increase in expression of major histocompatibility complex II molecules on the surface of dendritic cells, an effect that is also observed upon incubation of mouse BM12 dendritic cells with transgenic T cells whose T cell receptor is specific for the I-A(bm12) protein. Based on the present results, we suggest that activation of the RyR1 signaling cascade may be important in the early stages of infection, providing the immune system with a rapid mechanism to initiate an early response, facilitating the presentation of antigens to T cells by dendritic cells before their full maturation.
树突状细胞表达骨骼肌兰尼碱受体(RyR1),但其生理作用和激活机制仍知之甚少。在此我们表明,树突状细胞还表达L型钙通道的Ca(v)1.2亚基,并且通过RyR1释放细胞内Ca(2+)依赖于细胞外Ca(2+)的存在,且对兰尼碱和硝苯地平敏感。有趣的是,RyR1激活会导致树突状细胞表面主要组织相容性复合体II类分子的表达非常迅速地增加,在用其T细胞受体对I-A(bm12)蛋白具有特异性的转基因T细胞孵育小鼠BM12树突状细胞时也观察到这种效应。基于目前的结果,我们认为RyR1信号级联的激活在感染早期阶段可能很重要,为免疫系统提供一种快速机制来启动早期反应,促进树突状细胞在完全成熟之前将抗原呈递给T细胞。