Microglia are the resident immune cells of the CNS that are activated in response to a variety of stimuli. This phenotypical change is aimed to maintain the local homeostasis, also by containing the insults and repair the damages. All these processes are tightly regulated and coordinated and a failure in restoring homeostasis by microglia can result in the development of neuroinflammation that can facilitate the progression of pathological conditions. Indeed, chronic microglia activation is commonly recognized as a hallmark of many neurological disorders, especially at an early stage. Many complex pathways, including cytoskeletal remodeling, are involved in the control of the microglial phenotypical and morphological changes that occur during activation. In this work, we focused on the small GTPase Gα13 and its role at the crossroad between RhoA and Rac1 signaling when microglia is exposed to pro-inflammatory stimulation. We propose the direct involvement of Gα13 in the cytoskeletal rearrangements mediated by FAK, LIMK/cofilin, and Rac1 during microglia activation. In fact, we show that Gα13 knockdown significantly inhibited LPS-induced microglial cell activation, in terms of both changes in morphology and migration, through the modulation of FAK and one of its downstream effectors, Rac1. In conclusion, we propose Gα13 as a critical factor in the regulation of morphological and functional properties of microglia during activation, which might become a target of intervention for the control of microglia inflammation.

小胶质细胞是中枢神经系统的常驻免疫细胞，可响应各种刺激而被激活。这种表型变化旨在维持局部稳态，也通过控制损伤和修复损伤。所有这些过程都受到严格调节和协调，小胶质细胞无法恢复体内平衡会导致神经炎症的发展，从而促进病理状况的进展。事实上，慢性小胶质细胞激活通常被认为是许多神经系统疾病的标志，尤其是在早期阶段。许多复杂的途径，包括细胞骨架重塑，都参与了激活过程中发生的小胶质细胞表型和形态学变化的控制。在这项工作中，我们专注于小 GTPase Gα13 及其在小胶质细胞受到促炎刺激时在 RhoA 和 Rac1 信号转导之间的作用。我们建议 Gα13 在小胶质细胞激活过程中直接参与 FAK、LIMK/cofilin 和 Rac1 介导的细胞骨架重排。事实上，我们表明 Gα13 敲低通过调节 FAK 及其下游效应子 Rac1 显着抑制 LPS 诱导的小胶质细胞活化，无论是形态变化还是迁移。总之，我们提出 Gα13 作为调节小胶质细胞激活过程中形态和功能特性的关键因素，可能成为控制小胶质细胞炎症的干预目标。我们建议 Gα13 在小胶质细胞激活过程中直接参与 FAK、LIMK/cofilin 和 Rac1 介导的细胞骨架重排。事实上，我们表明 Gα13 敲低通过调节 FAK 及其下游效应子 Rac1 显着抑制 LPS 诱导的小胶质细胞活化，无论是形态变化还是迁移。总之，我们提出 Gα13 作为调节小胶质细胞激活过程中形态和功能特性的关键因素，可能成为控制小胶质细胞炎症的干预目标。我们建议 Gα13 在小胶质细胞激活过程中直接参与 FAK、LIMK/cofilin 和 Rac1 介导的细胞骨架重排。事实上，我们表明 Gα13 敲低通过调节 FAK 及其下游效应子 Rac1 显着抑制 LPS 诱导的小胶质细胞活化，无论是形态变化还是迁移。总之，我们提出 Gα13 作为调节小胶质细胞激活过程中形态和功能特性的关键因素，可能成为控制小胶质细胞炎症的干预目标。就形态和迁移的变化而言，通过调节 FAK 及其下游效应器之一 Rac1。总之，我们提出 Gα13 作为激活过程中调节小胶质细胞形态和功能特性的关键因素，可能成为控制小胶质细胞炎症的干预目标。就形态和迁移的变化而言，通过调节 FAK 及其下游效应器之一 Rac1。总之，我们提出 Gα13 作为调节小胶质细胞激活过程中形态和功能特性的关键因素，可能成为控制小胶质细胞炎症的干预目标。