Coordinated integrin activation by actin-dependent force during T-cell migration.
Coordinated integrin activation by actin-dependent force during T-cell migration.
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DOI：
10.1038/ncomms13119
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发表时间：
2016-10-10
影响因子：
16.6
通讯作者：
Springer, Timothy A.
中科院分区：
文献类型：
--
作者：
Nordenfelt, Pontus;Elliott, Hunter L.;Springer, Timothy A.
为了让细胞向前移动，它必须将化学能转化为机械推进。肌动蛋白聚合产生的力可以通过整合素传递到它们的配体，从而产生穿过质膜的牵引力。然而，这种力量在整合素激活中所起的作用尚不清楚。在这里，我们表明整合素活性和细胞骨架动力学是相互联系的，其中肌动蛋白依赖力本身似乎调节整合素活性。我们构建了整合素αLβ2(LFA-1)的荧光张力传感结构，以可视化细胞迁移过程中的分子内张力。利用迁移T细胞的定量成像，我们将αL或β2亚单位的张力与细胞和肌动蛋白动力学联系起来。我们发现，肌动蛋白的参与在β2亚单位内产生张力，以诱导和稳定活跃的整合素构象状态，这需要完整的Talin和kindlin基序。这支持了一种普遍的机制，在这种机制中，局部肌动蛋白聚合可以协调细胞迁移所需的复杂机制的激活。力在激活整合素细胞黏附受体中的作用尚不清楚。在这里，作者开发了针对αL和β2整合素的荧光张力传感器，并表明在迁移的T细胞中，力通过β2整合素传递，并且这与活跃的构象状态相关。
For a cell to move forward it must convert chemical energy into mechanical propulsion. Force produced by actin polymerization can generate traction across the plasma membrane by transmission through integrins to their ligands. However, the role this force plays in integrin activation is unknown. Here we show that integrin activity and cytoskeletal dynamics are reciprocally linked, where actin-dependent force itself appears to regulate integrin activity. We generated fluorescent tension-sensing constructs of integrin αLβ2 (LFA-1) to visualize intramolecular tension during cell migration. Using quantitative imaging of migrating T cells, we correlate tension in the αL or β2 subunit with cell and actin dynamics. We find that actin engagement produces tension within the β2 subunit to induce and stabilize an active integrin conformational state and that this requires intact talin and kindlin motifs. This supports a general mechanism where localized actin polymerization can coordinate activation of the complex machinery required for cell migration. The role of force in activating integrin cell adhesion receptors is not known. Here the authors develop fluorescent tension sensors for αL and β2 integrins and show that in migrating T cells force is transduced across the β2 integrin, and that this correlates with an active conformational state.
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影响因子：
56.9
作者：
Hu, Ke;Ji, Lin;Waterman-Storer, Clare M.
通讯作者：
Waterman-Storer, Clare M.
影响因子：
2.9
作者：
Astrof, Nathan S.;Salas, Azucena;Springer, Timothy A.
通讯作者：
Springer, Timothy A.
影响因子：
56.9
作者：
Kim, M;Carman, CV;Springer, TA
通讯作者：
Springer, TA
DOI：
10.1002/cyto.990060202
发表时间：
1985-01-01
期刊：
CYTOMETRY
影响因子：
--
作者：
GROEN, FCA;YOUNG, IT;LIGTHART, G
通讯作者：
LIGTHART, G
影响因子：
6.4
作者：
ANDERSON, DC;SCHMALSTEIG, FC;SPRINGER, TA
通讯作者：
SPRINGER, TA