The actin-bundling protein L-plastin dissociates CCR7 proximal signaling from CCR7-induced motility.
The actin-bundling protein L-plastin dissociates CCR7 proximal signaling from CCR7-induced motility.
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DOI：
10.4049/jimmunol.0903851
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发表时间：
2010-04-01
期刊：
影响因子：
--
通讯作者：
Allen PM
中科院分区：
文献类型：
--
作者：
Morley SC;Wang C;Lo WL;Lio CW;Zinselmeyer BH;Miller MJ;Brown EJ;Allen PM
趋化因子通过触发F-肌动蛋白重排和诱导细胞极化促进淋巴细胞运动。趋化因子还可以增强细胞-细胞粘附并共刺激T细胞。在这里，我们使用LPL −/−小鼠建立了CCR7和S1P1介导的T细胞趋化性对肌动蛋白捆绑蛋白L-纤维蛋白（LPL）的需求。在体内，成熟LPL −/−胸腺细胞的运动障碍表现为胸腺排出减少。LPL −/−淋巴细胞的双光子显微镜显示淋巴结中的速度和运动性降低。缺陷的迁移是由于CCR7连接后细胞极化缺陷造成的，因为CCR7在趋化因子刺激的LPL −/− T细胞中没有迁移到前沿。然而，在LPL −/−淋巴细胞中，CCR7信号传导至F-actin聚合和CCR7介导的共刺激是完整的。在CCR7诱导的细胞粘附和CCR7诱导的运动中对LPL的不同要求允许评估CCR7介导的运动对胸腺细胞阳性选择和谱系定型的贡献。结果表明，正常的运动是不需要CCR7的积极选择和谱系承诺的功能。因此，我们确定LPL作为CCR7介导的运动性的关键分子，但对早期CCR7信号传导是不重要的。肌动蛋白成束的LPL极化的要求揭示了一种新的机制，调节肌动蛋白的动态在T细胞运动。
Chemokines promote lymphocyte motility by triggering F-actin rearrangements and inducing cellular polarization. Chemokines can also enhance cell-cell adhesion and co-stimulate T cells. Here we establish a requirement for the actin-bundling protein L-plastin (LPL) in CCR7- and S1P1-mediated T cell chemotaxis using LPL−/− mice. Disrupted motility of mature LPL−/− thymocytes manifested in vivo as diminished thymic egress. Two-photon microscopy of LPL−/− lymphocytes revealed reduced velocity and motility in lymph nodes. Defective migration resulted from defective cellular polarization following CCR7 ligation, as CCR7 did not polarize to the leading edge in chemokine-stimulated LPL−/− T cells. However, CCR7 signaling to F-actin polymerization and CCR7-mediated co-stimulation was intact in LPL−/− lymphocytes. The differential requirement for LPL in CCR7-induced cellular adhesion and CCR7-induced motility allowed assessment of the contribution of CCR7-mediated motility to thymocyte positive selection and lineage commitment. Results suggest that normal motility is not required for CCR7 to function in positive selection and lineage commitment. We thus identify LPL as a molecule critical for CCR7-mediated motility but dispensable for early CCR7 signaling. The requirement for actin-bundling by LPL for polarization reveals a novel mechanism of regulating actin dynamics during T cell motility.
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影响因子：
7.8
作者：
Gerard, Audrey;Mertens, Alexander E E;van der Kammen, Rob A;Collard, John G
通讯作者：
Collard, John G
影响因子：
20.3
作者：
Davalos-Misslitz, Ana C. M.;Worbs, Tim;Foerster, Reinhold
通讯作者：
Foerster, Reinhold
影响因子：
32.4
作者：
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通讯作者：
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影响因子：
4.8
作者：
Jones, SL;Brown, EJ
通讯作者：
Brown, EJ
DOI：
10.1083/jcb.127.6.1995
发表时间：
1994-12
期刊：
The Journal of cell biology
影响因子：
--
作者：
Arpin M;Friederich E;Algrain M;Vernel F;Louvard D
通讯作者：
Louvard D