Age-related defects in moesin/ezrin cytoskeletal signals in mouse CD4 T cells
Age-related defects in moesin/ezrin cytoskeletal signals in mouse CD4 T cells
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DOI：
10.4049/jimmunol.179.10.6403
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发表时间：
2007-11-15
影响因子：
4.4
通讯作者：
Miller, Richard A.
中科院分区：
文献类型：
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作者：
Garcia, Gonzalo G.;Akha, Amir A. Sadighi;Miller, Richard A.
埃兹蛋白-根蛋白-膜突蛋白（ERM）家族的细胞骨架蛋白有助于响应于Ag的T细胞活化，并且还有助于响应于结缔组织基质蛋白和趋化因子梯度的T细胞极化。以前的工作已经表明，来自老年小鼠的T细胞在表面大分子和底层细胞骨架框架之间形成分子连接的能力方面存在缺陷，无论是移动到突触的蛋白质还是从T细胞-APC相互作用位点排除的蛋白质。当与涂有TCR/CD 3复合物抗体的载玻片接触时，老年小鼠的T细胞也显示出有缺陷的细胞骨架重排和片状伪足形成。在这项研究中，我们表明，老年CD 4 T细胞不同于年轻的CD 4 T细胞在几个方面的ERM生物化学，包括ERM磷酸化和ERM协会与CD 44，CD 43，和EBP 50。此外，来自老年小鼠的CD 4 T细胞显示出已知控制ERM功能的Rho GT3活性的缺陷。
Cytoskeletal proteins of the ezrin-radixin-moesin (ERM) family contribute to T cell activation in response to Ag, and also to T cell polarization in response to connective tissue matrix proteins and chemokine gradients. Previous work has shown that T cells from aged mice are defective in their ability to develop molecular linkages between surface macromolecules and the underlying cytoskeletal framework, both for proteins that move to the synapse and those that are excluded from the site of T cell-APC interaction. T cells from aged mice also show defective cytoskeletal rearrangements and lamellipodia formation when placed in contact with slides coated with Abs to the TCR/CD3 complex. In this study, we show that old CD4 T cells differ from young CD4 T cells in several aspects of ERM biochemistry, including ERM phosphorylation and ERM associations with CD44, CD43, and EBP50. In addition, CD4 T cells from aged mice show defects in the Rho GTPase activities known to control ERM function.