PD-LI promotes rear retraction during persistent cell migration by altering integrin β4 dynamics.
PD-LI promotes rear retraction during persistent cell migration by altering integrin β4 dynamics.
复制标题
DOI：
10.1083/jcb.202108083
复制
发表时间：
2022-05-02
期刊：
影响因子：
--
通讯作者：
Mercurio AM
中科院分区：
文献类型：
--
作者：
Wang M;Xiong C;Mercurio AM
这项研究揭示了PD-L1在调节质膜动力学方面的一种意想不到的细胞内在功能，这种功能有助于持续的细胞迁移。它强调了PD-L1可以独立于其免疫检查点功能调节的各种过程。虽然PD-L1的免疫检查点功能主导了其研究，但我们报告说PD-L1在促进持续细胞迁移的动力学方面具有意想不到的内在功能。PD-L1集中在迁移癌细胞的后部，在那里它促进回缩，导致形成含PD-L1的回缩纤维和移行体。PD-L1通过与β4整联蛋白相互作用并将其定位于后部，使该整联蛋白能够刺激收缩性，从而促进收缩。该机制涉及PD-L1维持细胞极性并降低细胞后部膜张力（与促进PD-L1和β4整联蛋白局部相互作用的前沿相比）的能力。这种相互作用使得β4整联蛋白能够接合肌动蛋白细胞骨架并促进RhoA介导的收缩性。这些发现对PD-L1的细胞自主功能和癌症生物学的影响是重要的。
This study reveals an unexpected cell-intrinsic function of PD-L1 in regulating the dynamics of the plasma membrane that facilitates persistent cell migration. It highlights the diverse processes that PD-L1 can regulate independently of its immune checkpoint function. Although the immune checkpoint function of PD-L1 has dominated its study, we report that PD-L1 has an unanticipated intrinsic function in promoting the dynamics of persistent cell migration. PD-L1 concentrates at the rear of migrating carcinoma cells where it facilitates retraction, resulting in the formation of PD-L1–containing retraction fibers and migrasomes. PD-L1 promotes retraction by interacting with and localizing the β4 integrin to the rear enabling this integrin to stimulate contractility. This mechanism involves the ability of PD-L1 to maintain cell polarity and lower membrane tension at the cell rear compared with the leading edge that promotes the localized interaction of PD-L1 and the β4 integrin. This interaction enables the β4 integrin to engage the actin cytoskeleton and promote RhoA-mediated contractility. The implications of these findings with respect to cell-autonomous functions of PD-L1 and cancer biology are significant.
登录
查看更多内容
影响因子：
6.4
作者：
Day CA;Kenworthy AK
通讯作者：
Kenworthy AK
迁移体为斑马鱼原肠胚形成期间的器官形态发生提供区域线索
影响因子：
21.3
作者：
Jiang, Dong;Jiang, Zheng;Yu, Li
通讯作者：
Yu, Li
影响因子：
--
作者：
KENNEL, SJ;EPLER, RG;SACCHI, A
通讯作者：
SACCHI, A
影响因子：
64.5
作者：
CAPCO, DG;WAN, KM;PENMAN, S
通讯作者：
PENMAN, S
影响因子：
20.3
作者：
Liu, Yin;Belkina, Natalya V.;Shaw, Stephen
通讯作者：
Shaw, Stephen