The Actin Cytoskeleton: A Mechanical Intermediate for Signal Integration at the Immunological Synapse.
The Actin Cytoskeleton: A Mechanical Intermediate for Signal Integration at the Immunological Synapse.
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DOI：
10.3389/fcell.2018.00116
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发表时间：
2018
影响因子：
5.5
通讯作者：
Burkhardt JK
中科院分区：
文献类型：
--
作者：
Roy NH;Burkhardt JK
免疫突触 (IS) 是一种特殊结构，充当 T 细胞和抗原呈递细胞 (APC) 之间细胞间通讯的平台。 T 细胞受体 (TCR) 与 APC 上的同源肽-MHC 复合物结合，激活 T 细胞并指示其分化。正确的 T 细胞激活还需要额外的受体-配体对的参与，从而促进持续粘附并传递共刺激信号。这些事件由 T 细胞肌动蛋白动力学精心策划，T 细胞肌动蛋白动力学组织 IS 组件并促进其信号传导。肌动蛋白网络从细胞边缘向内流动，驱动TCR微簇集中，并提供激活整合素LFA-1的力量。我们最近表明，LFA-1 的参与会减慢肌动蛋白流动，从而影响 TCR 信号传导。这项研究强调了 IS 的物理性质，并有助于该领域日益认识到机械传感和机械转导对于 IS 功能至关重要。此外，越来越清楚的是，IS 上有多种类型的肌动蛋白结构，它们以不同的方式促进信号传导。不同的肌动蛋白结构如何促进力的产生和力传导才刚刚开始被探索。在本视角中，我们将重点介绍我们实验室和其他实验室的最新工作，这些工作共同指向一个模型，在该模型中，肌动蛋白动力学在 T 细胞激活过程中驱动机械信号传导和受体串扰。
The immunological synapse (IS) is a specialized structure that serves as a platform for cell-cell communication between a T cell and an antigen-presenting cell (APC). Engagement of the T cell receptor (TCR) with cognate peptide-MHC complexes on the APC activates the T cell and instructs its differentiation. Proper T cell activation also requires engagement of additional receptor-ligand pairs, which promote sustained adhesion and deliver costimulatory signals. These events are orchestrated by T cell actin dynamics, which organize IS components and facilitate their signaling. The actin network flows from the edge of the cell inward, driving the centralization of TCR microclusters and providing the force to activate the integrin LFA-1. We recently showed that engagement of LFA-1 slows actin flow, and that this affects TCR signaling. This study highlights the physical nature of the IS, and contributes to a growing appreciation in the field that mechanosensing and mechanotransduction are essential for IS function. Additionally, it is becoming clear that there are multiple types of actin structures at the IS that promote signaling in distinct ways. How the different actin structures contribute to force production and mechanotransduction is just beginning to be explored. In this Perspective, we will feature recent work from our lab and others, that collectively points toward a model in which actin dynamics drive mechanical signaling and receptor crosstalk during T cell activation.
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影响因子：
21.3
作者：
Case LB;Waterman CM
通讯作者：
Waterman CM
DOI：
10.1083/jcb.201406120
发表时间：
2015-02-16
期刊：
The Journal of cell biology
影响因子：
--
作者：
Comrie WA;Li S;Boyle S;Burkhardt JK
通讯作者：
Burkhardt JK
DOI：
10.1083/jcb.201406121
发表时间：
2015-02-16
期刊：
The Journal of cell biology
影响因子：
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作者：
Comrie WA;Babich A;Burkhardt JK
通讯作者：
Burkhardt JK
DOI：
10.1083/jcb.201201018
发表时间：
2012-06-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Babich A;Li S;O'Connor RS;Milone MC;Freedman BD;Burkhardt JK
通讯作者：
Burkhardt JK
影响因子：
3.4
作者：
Judokusumo, Edward;Tabdanov, Erdem;Kam, Lance C.
通讯作者：
Kam, Lance C.