HLA-G is found in lipid rafts and can act as a signaling molecule
HLA-G is found in lipid rafts and can act as a signaling molecule
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DOI：
10.1016/j.humimm.2006.09.005
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发表时间：
2007-01-01
期刊：
影响因子：
2.7
通讯作者：
Warner, Carol M.
中科院分区：
文献类型：
--
作者：
Comiskey, Martina;Domino, Kenneth E.;Warner, Carol M.
人类白细胞抗原-G蛋白是小鼠着床前胚胎发育基因Qa-2的功能同源物。与表达Qa-2的胚胎相比，在细胞表面表达Qa-2的胚胎表现出更快的着床前卵裂速度和子宫内的优先存活。QA-2是连接在细胞膜上的糖基磷脂酰肌醇(GPI)。因此，Qa-2蛋白聚集在细胞膜中富含胆固醇和鞘磷脂的脂筏微域中，并可以通过RAFT相关的细胞内信号分子发出信号。以T细胞为模型系统，Qa-2在细胞膜上的交联可诱导静息细胞的增殖。与Qa-2一样，人类白细胞抗原-G缺乏能够将信号从细胞表面传递到细胞核的细胞质结构域，但与Qa-2不同的是，人类白细胞抗原-G有一个较短的六个氨基酸的细胞质尾巴，而不是GPI锚点。为了测试人类白细胞抗原-G是否像Qa-2一样位于脂筏中并且可以作为信号分子，我们使用了一个人类白细胞抗原-G转基因小鼠系统。分离T细胞，免疫荧光法检测人类白细胞抗原-G的表达，免疫荧光和免疫印迹法检测人类白细胞抗原-G在脂筏中的定位。然后，将T细胞与抗人类白细胞抗原-G抗体进行交联，以检测其是否具有促增殖作用。我们的新结果表明，与GPI连接的Qa-2一样，人类白细胞抗原-G存在于细胞膜的脂筏中，并可以作为信号分子诱导静止T细胞的增殖。
HLA-G protein is the functional homolog of Qa-2, the product of the mouse preimplantation embryo development (Ped) gene. Embryos expressing Qa-2 on the cell surface exhibit a faster rate of preimplantation cleavage and preferential survival in utero compared with Qa-2-negative embryos. Qa-2 is glycosylphosphatidylinositol (GPI) linked in the cell membrane. As a result, Qa-2 proteins cluster in cholesterol- and sphingolipid-rich lipid raft microdomains in the cell membrane and can signal via raft-associated intracellular signaling molecules. Using T cells as a model system, cross-linking of Qa-2 on the cell membrane has been shown to induce proliferation of resting cells. HLA-G, like Qa-2, lacks a cytoplasmic domain capable of transducing signals from the cell surface to the nucleus, but unlike Qa-2, HLA-G has a short six-amino acid cytoplasmic tail rather than a GPI anchor. To test whether HLA-G, like Qa-2, is located in lipid rafts and can act as a signaling molecule, we used an HLA-G transgenic mouse system. T cells were isolated and tested for HLA-G expression by immunofluorescence and for localization of HLA-G in lipid rafts by immunofluorescence and Western blotting. Next, the T cells were cross-linked with anti-HLA-G antibody to test for induction of proliferation. Our novel results show that HLA-G, like GPI-linked Qa-2, is present in lipid rafts in the cell membrane and can act as a signaling molecule to induce proliferation of resting T cells.