Adipocyte differentiation is accompanied by a pronounced change in the actin cytoskeleton characterized by the reorganization of filamentous (F)-actin stress fibers into cortical F-actin structures. We previously showed that depolymerization of F-actin stress fibers induced by inactivation of RhoA-ROCK (Rho-associated kinase) signaling acts as a trigger for adipocyte differentiation. The relevance and underlying mechanism of the formation of cortical F-actin structures from depolymerized actin during adipocyte differentiation have remained unclear, however. We have now examined the mechanistic relation between actin dynamics and adipogenic induction. Transient exposure to the actin-depolymerizing agent latrunculin A (LatA) supported the formation of adipocyte-associated cortical actin structures and the completion of terminal adipocyte differentiation in the presence of insulin, whereas long-term exposure to LatA prevented such actin reorganization as well as terminal adipogenesis. Moreover, these effects of insulin were prevented by inhibition of phosphatidylinositol 3-kinase (PI3K)-Rac1 signaling and the actin-related protein 2/3 (Arp2/3) complex which is a critical component of the cortical actin networks. Our findings thus suggest that the insulin-PI3K-Rac1 axis leads to the formation of adipocyte-associated cortical actin structures which is essential for the completion of adipocyte differentiation.

中文翻译：

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胰岛素-PI3K-Rac1轴通过调节肌动蛋白细胞骨架动力学来促进终末脂肪细胞分化。

脂肪细胞的分化伴随着肌动蛋白细胞骨架的显着变化，其特征是丝状（F）-肌动蛋白应激纤维重组为皮质F-肌动蛋白结构。我们以前表明，通过失活RhoA-ROCK（Rho相关激酶）信号转导诱导的F-肌动蛋白应力纤维的解聚充当脂肪细胞分化的触发因素。然而，尚不清楚脂肪细胞分化过程中解聚的肌动蛋白形成皮质F-肌动蛋白结构的相关性和潜在机制。现在我们已经研究了肌动蛋白动力学和成脂诱导之间的机制关系。肌动蛋白解聚剂latrunculin A（LatA）的短暂暴露支持在胰岛素存在下脂肪细胞相关的皮质肌动蛋白结构的形成和最终脂肪细胞分化的完成，而长期暴露于LatA则阻止了这种肌动蛋白的重组以及晚期脂肪形成。此外，通过抑制磷脂酰肌醇3-激酶（PI3K）-Rac1信号转导和肌动蛋白相关蛋白2/3（Arp2 / 3）复合物（是皮质肌动蛋白网络的关键组成部分），可以防止胰岛素的这些作用。因此，我们的发现表明，胰岛素-PI3K-Rac1轴导致形成与脂肪细胞相关的皮质肌动蛋白结构，这对于完成脂肪细胞的分化至关重要。而长期暴露于LatA则阻止了这种肌动蛋白的重组以及最终的脂肪形成。此外，通过抑制磷脂酰肌醇3-激酶（PI3K）-Rac1信号转导和肌动蛋白相关蛋白2/3（Arp2 / 3）复合物（是皮质肌动蛋白网络的关键组成部分），可以防止胰岛素的这些作用。因此，我们的发现表明，胰岛素-PI3K-Rac1轴导致形成与脂肪细胞相关的皮质肌动蛋白结构，这对于完成脂肪细胞的分化至关重要。而长期暴露于LatA则阻止了这种肌动蛋白的重组以及最终的脂肪形成。此外，通过抑制磷脂酰肌醇3-激酶（PI3K）-Rac1信号转导和肌动蛋白相关蛋白2/3（Arp2 / 3）复合物（是皮质肌动蛋白网络的关键组成部分），可以防止胰岛素的这些作用。因此，我们的发现表明，胰岛素-PI3K-Rac1轴导致形成与脂肪细胞相关的皮质肌动蛋白结构，这对于完成脂肪细胞的分化至关重要。