当前位置: X-MOL 学术J. Cell Sci. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
LFA-1 signals to promote actin polymerization and upstream migration in T cells.
Journal of Cell Science ( IF 4 ) Pub Date : 2020-09-09 , DOI: 10.1242/jcs.248328
Nathan H Roy 1 , Sarah Hyun Ji Kim 2 , Alexander Buffone 3 , Daniel Blumenthal 1 , Bonnie Huang 4, 5 , Sangya Agarwal 6 , Pamela L Schwartzberg 4, 5 , Daniel A Hammer 2, 3 , Janis K Burkhardt 6, 7
Affiliation  

Nathan H. Roy, Sarah Hyun Ji Kim, Alexander Buffone Jr, Daniel Blumenthal, Bonnie Huang, Sangya Agarwal, Pamela L. Schwartzberg, Daniel A. Hammer, and Janis K. Burkhardt

T cell entry into inflamed tissue requires firm adhesion, cell spreading, and migration along and through the endothelial wall. These events require the T cell integrins LFA-1 and VLA-4 and their endothelial ligands ICAM-1 and VCAM-1, respectively. T cells migrate against the direction of shear flow on ICAM-1 and with the direction of shear flow on VCAM-1, suggesting that these two ligands trigger distinct cellular responses. However, the contribution of specific signaling events downstream of LFA-1 and VLA-4 has not been explored. Using primary mouse T cells, we found that engagement of LFA-1, but not VLA-4, induces cell shape changes associated with rapid 2D migration. Moreover, LFA-1 ligation results in activation of the phosphoinositide 3-kinase (PI3K) and ERK pathways, and phosphorylation of multiple kinases and adaptor proteins, whereas VLA-4 ligation triggers only a subset of these signaling events. Importantly, T cells lacking Crk adaptor proteins, key LFA-1 signaling intermediates, or the ubiquitin ligase cCbl (also known as CBL), failed to migrate against the direction of shear flow on ICAM-1. These studies identify novel signaling differences downstream of LFA-1 and VLA-4 that drive T cell migratory behavior.

This article has an associated First Person interview with the first author of the paper.



中文翻译:

LFA-1 信号促进 T 细胞中肌动蛋白聚合和上游迁移。

Nathan H. Roy、Sarah Hyun Ji Kim、Alexander Buffone Jr、Daniel Blumenthal、Bonnie Huang、Sangya Agarwal、Pamela L. Schwartzberg、Daniel A. Hammer 和 Janis K. Burkhardt

T 细胞进入发炎组织需要牢固的粘附、细胞扩散以及沿着和穿过内皮壁的迁移。这些事件分别需要 T 细胞整合素 LFA-1 和 VLA-4 及其内皮配体 ICAM-1 和 VCAM-1。T 细胞逆着 ICAM-1 上的剪切流方向迁移,并沿着 VCAM-1 上的剪切流方向迁移,表明这两种配体触发不同的细胞反应。然而,LFA-1 和 VLA-4 下游特定信号事件的贡献尚未被探索。使用原代小鼠 T 细胞,我们发现 LFA-1(而非 VLA-4)的参与会诱导与快速 2D 迁移相关的细胞形状变化。此外,LFA-1 连接导致磷酸肌醇 3 激酶 (PI3K) 和 ERK 通路的激活,以及多种激酶和接头蛋白的磷酸化,而 VLA-4 连接仅触发这些信号传导事件的子集。重要的是,缺乏 Crk 接头蛋白、关键的 LFA-1 信号传导中间体或泛素连接酶 cCbl(也称为 CBL)的 T 细胞无法逆着 ICAM-1 上的剪切流方向迁移。这些研究确定了 LFA-1 和 VLA-4 下游驱动 T 细胞迁移行为的新信号传导差异。

本文有对该论文第一作者的相关第一人称采访。

更新日期:2020-09-15
down
wechat
bug