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Bcl10 is associated with actin dynamics at the T cell immune synapse.
Cellular Immunology ( IF 3.7 ) Pub Date : 2020-07-15 , DOI: 10.1016/j.cellimm.2020.104161
Kaustubh Wagh 1 , Brittany A Wheatley 2 , Maria K Traver 3 , Imran Hussain 3 , Brian C Schaefer 3 , Arpita Upadhyaya 4
Affiliation  

T cell responses to antigen are initiated by engagement of the T cell receptor (TCR)1, leading to activation of diverse signaling cascades, including an incompletely defined pathway that triggers rapid remodeling of the actin cytoskeleton. Defects in the control of actin dynamics and organization are associated with several human immunodeficiency diseases, emphasizing the importance of cytoskeletal remodeling in the functioning of the adaptive immune system. Here, we investigate the role of the adaptor protein Bcl102 in the control of actin dynamics. Although Bcl10 is primarily known as a component of the pathway connecting the TCR to activation of the NF-κB3 transcription factor, a few studies have implicated Bcl10 in antigen receptor-dependent control of actin polymerization and F-actin-dependent functional responses. However, the role of Bcl10 in the regulation of cytoskeletal dynamics remains largely undefined. To investigate the contribution of Bcl10 in the regulation of TCR-dependent cytoskeletal dynamics, we monitored actin dynamics at the immune synapse of primary murine CD8 effector T cells. Quantification of these dynamics reveals two distinct temporal phases distinguished by differences in speed and directionality. Our results indicate that effector CD8 T cells lacking Bcl10 display faster actin flows and more dynamic lamellipodia, compared to wild-type cells. These studies define a role for Bcl10 in TCR-dependent actin dynamics, emphasizing that Bcl10 has important cytoskeleton-directed functions that are likely independent of its role in transmission of NF-κB -activating signals.



中文翻译:

Bcl10 与 T 细胞免疫突触的肌动蛋白动力学有关。

T 细胞对抗原的反应是由 T 细胞受体 (TCR) 1 的参与启动的,导致激活不同的信号级联,包括触发肌动蛋白细胞骨架快速重塑的不完全定义的途径。肌动蛋白动力学和组织的控制缺陷与几种人类免疫缺陷疾病有关,强调了细胞骨架重塑在适应性免疫系统功能中的重要性。在这里,我们调查了适配器蛋白 Bcl10 2在控制肌动蛋白动力学中的作用。尽管 Bcl10 主要被认为是将 TCR 与 NF-κB 激活连接起来的通路的一个组成部分3转录因子,一些研究表明 Bcl10 参与抗原受体依赖性肌动蛋白聚合和 F-肌动蛋白依赖性功能反应的控制。然而,Bcl10 在细胞骨架动力学调节中的作用在很大程度上仍未确定。为了研究 Bcl10 在调节 TCR 依赖性细胞骨架动力学中的贡献,我们监测了原代小鼠 CD8 效应 T 细胞免疫突触的肌动蛋白动力学。这些动态的量化揭示了两个不同的时间阶段,其区别在于速度和方向性的差异。我们的结果表明,与野生型细胞相比,缺乏 Bcl10 的效应 CD8 T 细胞显示出更快的肌动蛋白流动和更动态的片状伪足。这些研究定义了 Bcl10 在 TCR 依赖性肌动蛋白动力学中的作用,

更新日期:2020-08-06
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