当前位置: X-MOL 学术The Journal of Cell Biology › 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.)
Ubiquitylation by Rab40b/Cul5 regulates Rap2 localization and activity during cell migration
The Journal of Cell Biology Pub Date : 2022-03-16 , DOI: 10.1083/jcb.202107114
Emily D Duncan 1 , Ke-Jun Han 1 , Margaret A Trout 1 , Rytis Prekeris 1
Affiliation  

Cell migration is a complex process that involves coordinated changes in membrane transport and actin cytoskeleton dynamics. Ras-like small monomeric GTPases, such as Rap2, play a key role in regulating actin cytoskeleton dynamics and cell adhesions. However, how Rap2 function, localization, and activation are regulated during cell migration is not fully understood. We previously identified the small GTPase Rab40b as a regulator of breast cancer cell migration. Rab40b contains a suppressor of cytokine signaling (SOCS) box, which facilitates binding to Cullin5, a known E3 ubiquitin ligase component responsible for protein ubiquitylation. In this study, we show that the Rab40b/Cullin5 complex ubiquitylates Rap2. Importantly, we demonstrate that ubiquitylation regulates Rap2 activation as well as recycling of Rap2 from the endolysosomal compartment to the lamellipodia of migrating breast cancer cells. Based on these data, we propose that Rab40b/Cullin5 ubiquitylates and regulates Rap2-dependent actin dynamics at the leading edge, a process that is required for breast cancer cell migration and invasion.

中文翻译:

Rab40b/Cul5 的泛素化调节细胞迁移过程中 Rap2 的定位和活性

细胞迁移是一个复杂的过程,涉及膜运输和肌动蛋白细胞骨架动力学的协调变化。 Ras 样的小型单体 GTP 酶(例如 Rap2)在调节肌动蛋白细胞骨架动力学和细胞粘附方面发挥着关键作用。然而,Rap2 的功能、定位和激活在细胞迁移过程中是如何调节的尚不完全清楚。我们之前发现小 GTPase Rab40b 是乳腺癌细胞迁移的调节因子。 Rab40b 含有细胞因子信号传导抑制器 (SOCS) 盒,有助于与 Cullin5 结合,Cullin5 是一种已知的 E3 泛素连接酶成分,负责蛋白质泛素化。在这项研究中,我们证明 Rab40b/Cullin5 复合物泛素化 Rap2。重要的是,我们证明泛素化调节 Rap2 激活以及 Rap2 从内溶酶体区室到迁移乳腺癌细胞的板状伪足的再循环。基于这些数据,我们提出 Rab40b/Cullin5 在前沿泛素化并调节 Rap2 依赖性肌动蛋白动力学,这是乳腺癌细胞迁移和侵袭所需的过程。
更新日期:2022-03-16
down
wechat
bug