Rab40-Cullin5 complex regulates EPLIN and actin cytoskeleton dynamics during cell migration.
Rab40-Cullin5 complex regulates EPLIN and actin cytoskeleton dynamics during cell migration.
复制标题
Rab 40-Cullin 5复合物在细胞迁移过程中调节EPLIN和肌动蛋白细胞骨架动力学。
DOI：
10.1083/jcb.202008060
复制
发表时间：
2021-07-05
期刊：
影响因子：
--
通讯作者：
Prekeris R
中科院分区：
文献类型：
--
作者：
Linklater ES;Duncan ED;Han KJ;Kaupinis A;Valius M;Lyons TR;Prekeris R
这项研究表明，Rab40b与Cullin5相互作用，失去Rab40b-cullin5的结合会影响应力纤维的形成和局部黏附动力学。从机制上讲，这些作用部分是由EPLIN介导的，EPLIN是Rab40b-Cullin5依赖的局部泛素化和降解的靶标。Rab40b是一种含有SoCS盒的蛋白，调节MMPs的分泌，促进细胞迁移过程中细胞外基质的重塑。在这里，我们证明了Rab40b通过Rab40b SOCS结构域与Cullin5相互作用。我们证明，失去Rab40b-Cullin5结合降低了细胞的运动性和侵袭性，并表明缺陷的细胞迁移和侵袭源于肌动蛋白细胞骨架的改变，导致内陷形成减少，前沿肌动蛋白动力学降低，应力纤维增加。我们还表明，这些应力纤维锚定在较少的动态，更稳定的局灶性粘连。从机制上讲，细胞骨架和局部黏附动力学的变化部分是由EPLIN介导的，我们证明EPLIN是Rab40b的结合伙伴，也是Rab40b-Cullin5依赖的局部泛素化和降解的靶标。因此，我们提出了一个模型，其中Rab40b-cullin5依赖的泛素化调节EPLIN的定位，通过改变焦点黏附和细胞骨架动力学来促进细胞迁移和侵袭。
This study shows that Rab40b interacts with Cullin5 and that loss of Rab40b–Cullin5 binding affects stress fiber formation and focal adhesion dynamics. Mechanistically, these effects are mediated in part by EPLIN, which is a target for Rab40b–Cullin5-dependent localized ubiquitylation and degradation. Rab40b is a SOCS box–containing protein that regulates the secretion of MMPs to facilitate extracellular matrix remodeling during cell migration. Here, we show that Rab40b interacts with Cullin5 via the Rab40b SOCS domain. We demonstrate that loss of Rab40b–Cullin5 binding decreases cell motility and invasive potential and show that defective cell migration and invasion stem from alteration to the actin cytoskeleton, leading to decreased invadopodia formation, decreased actin dynamics at the leading edge, and an increase in stress fibers. We also show that these stress fibers anchor at less dynamic, more stable focal adhesions. Mechanistically, changes in the cytoskeleton and focal adhesion dynamics are mediated in part by EPLIN, which we demonstrate to be a binding partner of Rab40b and a target for Rab40b–Cullin5-dependent localized ubiquitylation and degradation. Thus, we propose a model where Rab40b–Cullin5-dependent ubiquitylation regulates EPLIN localization to promote cell migration and invasion by altering focal adhesion and cytoskeletal dynamics.
登录
查看更多内容
DOI：
10.1083/jcb.201508080
发表时间：
2016-02-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Horton ER;Humphries JD;Stutchbury B;Jacquemet G;Ballestrem C;Barry ST;Humphries MJ
通讯作者：
Humphries MJ
影响因子：
3.7
作者：
Burridge K;Guilluy C
通讯作者：
Guilluy C
影响因子：
1.9
作者：
Horzum, Utku;Ozdil, Berrin;Pesen-Okvur, Devrim
通讯作者：
Pesen-Okvur, Devrim
影响因子：
--
作者：
Berginski ME;Gomez SM
通讯作者：
Gomez SM
影响因子：
11.4
作者：
Bravo-Cordero, Jose J.;Marrero-Diaz, Raquel;Montoya, Maria C.
通讯作者：
Montoya, Maria C.