Experimental Immunology Branch, National Cancer Institute, Bethesda, MD, USA.
Blood. 2012 Jan 12;119(2):445-53. doi: 10.1182/blood-2011-07-368860. Epub 2011 Nov 21.
ERM (ezrin, radixin moesin) proteins in lymphocytes link cortical actin to plasma membrane, which is regulated in part by ERM protein phosphorylation. To assess whether phosphorylation of ERM proteins regulates lymphocyte migration and membrane tension, we generated transgenic mice whose T-lymphocytes express low levels of ezrin phosphomimetic protein (T567E). In these mice, T-cell number in lymph nodes was reduced by 27%. Lymphocyte migration rate in vitro and in vivo in lymph nodes decreased by 18% to 47%. Lymphocyte membrane tension increased by 71%. Investigations of other possible underlying mechanisms revealed impaired chemokine-induced shape change/lamellipod extension and increased integrin-mediated adhesion. Notably, lymphocyte homing to lymph nodes was decreased by 30%. Unlike most described homing defects, there was not impaired rolling or sticking to lymph node vascular endothelium but rather decreased migration across that endothelium. Moreover, decreased numbers of transgenic T cells in efferent lymph suggested defective egress. These studies confirm the critical role of ERM dephosphorylation in regulating lymphocyte migration and transmigration. Of particular note, they identify phospho-ERM as the first described regulator of lymphocyte membrane tension, whose increase probably contributes to the multiple defects observed in the ezrin T567E transgenic mice.
ERM（埃兹蛋白、根蛋白和膜突蛋白）蛋白在淋巴细胞中把皮质肌动蛋白与质膜连接起来，其功能部分受到 ERM 蛋白磷酸化的调节。为了评估 ERM 蛋白磷酸化是否调节淋巴细胞的迁移和膜张力，我们生成了表达低水平 ezrin 磷酸模拟蛋白（T567E）的转基因小鼠。在这些小鼠中，淋巴结中的 T 细胞数量减少了 27%。T 细胞在体外和体内淋巴结中的迁移率降低了 18%至 47%。T 细胞的膜张力增加了 71%。对其他可能的潜在机制的研究表明，这些小鼠的趋化因子诱导的形态变化/片状伪足延伸受损，整合素介导的黏附增加。值得注意的是，淋巴细胞归巢到淋巴结的数量减少了 30%。与大多数描述的归巢缺陷不同，这些小鼠不是滚动或黏附到淋巴结血管内皮细胞的能力受损，而是穿过内皮细胞的迁移能力降低。此外，流出淋巴管中转基因 T 细胞数量减少表明它们的迁出能力受损。这些研究证实了 ERM 去磷酸化在调节淋巴细胞迁移和穿越中的关键作用。值得注意的是，它们确定了磷酸化 ERM 是第一个描述的淋巴细胞膜张力调节剂，其增加可能导致在 ezrin T567E 转基因小鼠中观察到的多种缺陷。
