Moesin interacts with the cytoplasmic region of intercellular adhesion molecule-3 and is redistributed to the uropod of T lymphocytes during cell polarization.

Moesin interacts with the cytoplasmic region of intercellular adhesion molecule-3 and is redistributed to the uropod of T lymphocytes during cell polarization.
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Moesin与细胞间粘附分子-3的细胞质区域相互作用,并在细胞极化期间将其重新分布在T淋巴细胞的uropod中。

DOI:
10.1083/jcb.138.6.1409
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发表时间:
1997-09-22
影响因子:
7.8
通讯作者:
SanchezMadrid, F
SanchezMadrid, F
中科院分区:
生物学1区
文献类型:
--
作者:
Serrador, JM;AlonsoLebrero, JL;delPozo, MA;Furthmayr, H;SchwartzAlbiez, R;Calvo, J;Lozano, F;SanchezMadrid, F

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在激活过程中,T淋巴细胞变成运动细胞,从球形变为极化形状。趋化因子和其他趋化因子诱导淋巴细胞极化,在后极形成尾足,在那里粘附受体细胞间粘附分子-1 (ICAM-1)、ICAM-3和CD44重新分布。我们已经研究了膜-细胞骨架的相互作用,在粘连受体重新分配到尾足动物中起关键作用。免疫荧光分析显示,趋化因子RANTES(调节激活、正常T细胞的表达和分泌)诱导人T淋巴细胞后,ERM蛋白radixin和moesin定位于尾足;radixin与位于尾足动物颈部的肌球蛋白II阵列共定位,而moesin则装饰在尾足动物的最末端,并与ICAM-1、ICAM-3和CD44分子共定位。另外两种细胞骨架蛋白,β-肌动蛋白和α-微管蛋白,分别聚集在极化淋巴细胞的细胞边缘和尾足。生化分析表明,在RANTES或诱导极化的抗ICAM-3 HP2/19单抗刺激的T淋巴细胞以及组成极化的T细胞系HSB-2中,moesin与ICAM-3共免疫沉淀。此外,在极化T淋巴细胞中,moesin与CD44相关,而与ICAM-1无关。moesin-ICAM-3相互作用的程度与细胞极化之间存在相关性,通过免疫荧光和免疫沉淀分析同时进行。moesin - ICAM-3的相互作用是由ICAM-3的胞质结构域特异性介导的,这是由含有ICAM-3胞质尾部的GST融合蛋白沉淀的结果,这些融合蛋白来自代谢标记的Jurkat T细胞裂解物。当rantes刺激的T淋巴细胞被肌球蛋白干扰药物丁二酮单肟预处理时,moesin与ICAM-3的相互作用大大减弱,这种药物可以阻止淋巴细胞极化。总之,这些数据表明moesin在极化T细胞的尾足中与ICAM-3和CD44粘附分子相互作用;这些数据还表明,这些相互作用参与形成膜受体和细胞骨架之间的联系,从而调节细胞运动过程中的形态变化。
During activation, T lymphocytes become motile cells, switching from a spherical to a polarized shape. Chemokines and other chemotactic cytokines induce lymphocyte polarization with the formation of a uropod in the rear pole, where the adhesion receptors intercellular adhesion molecule-1 (ICAM-1), ICAM-3, and CD44 redistribute. We have investigated membrane–cytoskeleton interactions that play a key role in the redistribution of adhesion receptors to the uropod. Immunofluorescence analysis showed that the ERM proteins radixin and moesin localized to the uropod of human T lymphoblasts treated with the chemokine RANTES (regulated on activation, normal T cell expressed, and secreted), a polarization-inducing agent; radixin colocalized with arrays of myosin II at the neck of the uropods, whereas moesin decorated the most distal part of the uropod and colocalized with ICAM-1, ICAM-3, and CD44 molecules. Two other cytoskeletal proteins, β-actin and α-tubulin, clustered at the cell leading edge and uropod, respectively, of polarized lymphocytes. Biochemical analysis showed that moesin coimmunoprecipitates with ICAM-3 in T lymphoblasts stimulated with either RANTES or the polarization- inducing anti–ICAM-3 HP2/19 mAb, as well as in the constitutively polarized T cell line HSB-2. In addition, moesin is associated with CD44, but not with ICAM-1, in polarized T lymphocytes. A correlation between the degree of moesin–ICAM-3 interaction and cell polarization was found as determined by immunofluorescence and immunoprecipitation analysis done in parallel. The moesin–ICAM-3 interaction was specifically mediated by the cytoplasmic domain of ICAM-3 as revealed by precipitation of moesin with a GST fusion protein containing the ICAM-3 cytoplasmic tail from metabolically labeled Jurkat T cell lysates. The interaction of moesin with ICAM-3 was greatly diminished when RANTES-stimulated T lymphoblasts were pretreated with the myosin-disrupting drug butanedione monoxime, which prevents lymphocyte polarization. Altogether, these data indicate that moesin interacts with ICAM-3 and CD44 adhesion molecules in uropods of polarized T cells; these data also suggest that these interactions participate in the formation of links between membrane receptors and the cytoskeleton, thereby regulating morphological changes during cell locomotion.
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