文章：

ERRα协调肌动蛋白和焦点粘附动力学

ERRα coordinates actin and focal adhesion dynamics 

原文发布日期：2022-04-04 

英文摘要：

Cell migration depends on the dynamic organisation of the actin cytoskeleton and assembly and disassembly of focal adhesions (FAs). However, the precise mechanisms coordinating these processes remain poorly understood. We previously identified the oestrogen-related receptor α (ERRα) as a major regulator of cell migration. Here, we show that loss of ERRα leads to abnormal accumulation of actin filaments that is associated with an increased level of inactive form of the actin-depolymerising factor cofilin. We further show that ERRα depletion decreases cell adhesion and results in defective FA formation and turnover. Interestingly, specific inhibition of the RhoA-ROCK-LIMK-cofilin pathway rescues the actin polymerisation defects resulting from ERRα silencing, but not cell adhesion. Instead, we found that MAP4K4 is a direct target of ERRα and down-regulation of its activity rescues cell adhesion and FA formation in the ERRα-depleted cells. Altogether, our results highlight a crucial role of ERRα in coordinating the dynamic of actin network and FAs through the independent regulation of the RhoA and MAP4K4 pathways. 

摘要翻译： 

细胞迁移依赖于肌动蛋白细胞骨架的动态组织以及粘着斑（FAs）的组装与解组装过程。然而，协调这些过程的具体机制尚不明确。我们先前发现雌激素相关受体α（ERRα）是细胞迁移的主要调控因子。本研究表明，ERRα的缺失会导致肌动蛋白丝异常积聚，这与肌动蛋白解聚因子丝切蛋白失活形式的水平升高相关。我们进一步发现ERRα耗竭会降低细胞粘附能力，导致粘着斑形成和更新缺陷。值得注意的是，特异性抑制RhoA-ROCK-LIMK-丝切蛋白通路可挽救因ERRα沉默引起的肌动蛋白聚合缺陷，但无法改善细胞粘附。相反，我们发现MAP4K4是ERRα的直接靶标，下调其活性可挽救ERRα缺失细胞的粘附能力及粘着斑形成。综上所述，我们的研究结果揭示了ERRα通过独立调控RhoA和MAP4K4通路，在协调肌动蛋白网络与粘着斑动态变化中发挥关键作用。

原文链接：

ERRα coordinates actin and focal adhesion dynamics