Lipid rafts mediate biosynthetic transport to the T lymphocyte uropod subdomain and are necessary for uropod integrity and function
Lipid rafts mediate biosynthetic transport to the T lymphocyte uropod subdomain and are necessary for uropod integrity and function
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DOI：
10.1182/blood.v99.3.978
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发表时间：
2002-02-01
期刊：
影响因子：
20.3
通讯作者：
Alonso, MA
中科院分区：
文献类型：
--
作者：
Millán, J;Montoya, MC;Alonso, MA
极化迁移性T细胞具有两极，尾足突起在后部，前缘在前部，具有特定的蛋白质组成和功能。流感病毒血凝素（HA）是一种典型的分子，它利用脂质筏在极化的上皮Madin-Darby犬肾（MDCK）细胞中生物合成转运到顶端表面。在这项研究中，HA被用来作为一种工具，研究在极化T淋巴细胞的载体蛋白运输的脂质筏的作用。结果表明，新合成的HA成为选择性靶向极化T淋巴母细胞中的尾足亚结构域。HA在生物合成后不久并入筏中，这表明HA向尾足动物的递送是通过使人联想到用于其特异性靶向顶端表面的转运途径发生的。在T淋巴母细胞表面筏中检测到HA和细胞间粘附分子3（ICAM-3）、CD 44和CD 43 3 3种内源性尿足标记物。胆固醇是脂筏的主要成分，主要存在于尾足类中。破坏脂筏完整性的胆固醇螯合产生的ICAM-3和尿足的损失和严重受损的过程，需要一个极化的表型，如细胞间的聚集和细胞迁移的unclustering。总的来说，这些结果表明，脂筏构成了一条路线，选择性靶向蛋白质的尾足类和筏是必不可少的生成，维护和功能的T细胞前后极性。(C)2002年，美国血液学会。
Polarized migrating T cells possess 2 poles, the uropod protrusion at the rear and the leading edge at the front, with specific protein composition and function. The influenza virus hemagglutinin (HA) is a prototypical molecule that uses lipid rafts for biosynthetic transport to the apical surface in polarized epithelial Madin-Darby canine kidney (MDCK) cells. In this study, HA was used as a tool to Investigate the role of lipid rafts In vectorial protein traffic in polarized T lymphocytes. Results show that newly synthesized HA becomes selectively targeted to the uropod subdomain in polarized T lymphoblasts. HA incorporates into rafts soon after biosynthesis, suggesting that delivery of HA to the uropod occurs through a pathway of transport reminiscent of that used for its specific targeting to the apical surface. HA and the adhesion molecules, intercellular adhesion molecule 3 (ICAM-3), CD44, and CD43, 3 endogenous uropod markers, were detected in surface rafts of T lymphoblasts. Cholesterol, a major component of lipid rafts, was predominantly located in the uropod. Disruption of lipid raft integrity by cholesterol sequestration produced unclustering of ICAM-3 and the loss of uropodia and severely impaired processes that require a polarized phenotype such as Intercellular aggregation and cell migration. Collectively, these results Indicate that lipid rafts constitute a route for selective targeting of proteins to the uropod and that the rafts are essential for the generation, maintenance, and functionality of T-cell anteroposterior polarity. (C) 2002 by The American Society of Hematology.