Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto, Porto, Portugal.
Graduate Programme in Areas of Basic and Applied Biology (GABBA), Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, Porto, Portugal.
Glia. 2021 Nov;69(11):2717-2738. doi: 10.1002/glia.24067. Epub 2021 Jul 30.
The ramified morphology of microglia and the dynamics of their membrane protrusions are essential for their functions in central nervous system development, homeostasis, and disease. Although their ability to change and control shape critically depends on the actin and actomyosin cytoskeleton, the underlying regulatory mechanisms remain largely unknown. In this study, we systematically analyzed the actomyosin cytoskeleton and regulators downstream of the small GTPase RhoA in the control of microglia shape and function. Our results reveal that (i) Myh9 controls cortical tension levels and affects microglia protrusion formation, (ii) cofilin-mediated maintenance of actin turnover regulates microglia protrusion extension, and (iii) Myh10 influences microglia inflammatory activation. Overall we uncover molecular pathways that regulate microglia morphology and identify type-II myosins as important regulators of microglia biology with differential roles in the control of cell shape (Myh9) and functions (Myh10).
小胶质细胞的分支形态及其细胞膜突起的动态变化对于它们在中枢神经系统发育、稳态和疾病中的功能至关重要。尽管它们改变和控制形状的能力严重依赖于肌动蛋白和肌球蛋白细胞骨架，但潜在的调节机制在很大程度上仍然未知。在这项研究中，我们系统地分析了肌球蛋白细胞骨架和小 GTPase RhoA 下游的调节剂在控制小胶质细胞形状和功能中的作用。我们的结果表明：（i）Myh9 控制皮质张力水平并影响小胶质细胞突起的形成，（ii）肌动蛋白周转率的 cofilin 调节控制小胶质细胞突起的延伸，以及（iii）Myh10 影响小胶质细胞的炎症激活。总的来说，我们揭示了调节小胶质细胞形态的分子途径，并确定了 II 型肌球蛋白作为小胶质细胞生物学的重要调节剂，它们在控制细胞形状（Myh9）和功能（Myh10）方面具有不同的作用。
