The insulin-PI3K-Rac1 axis contributes to terminal adipocyte differentiation through regulation of actin cytoskeleton dynamics
The insulin-PI3K-Rac1 axis contributes to terminal adipocyte differentiation through regulation of actin cytoskeleton dynamics
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DOI：
10.1111/gtc.12747
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发表时间：
2020-01-29
期刊：
影响因子：
2.1
通讯作者：
Nobusue, Hiroyuki
中科院分区：
文献类型：
--
作者：
Kunitomi, Haruko;Oki, Yoshinao;Nobusue, Hiroyuki
脂肪细胞分化伴随着肌动蛋白细胞骨架的显著变化，其特征在于丝状（F）-肌动蛋白应力纤维重组成皮质F-肌动蛋白结构。我们以前表明，解聚的F-肌动蛋白应力纤维诱导的失活的RhoA-ROCK（Rho相关激酶）信号作为脂肪细胞分化的触发器。然而，在脂肪细胞分化过程中，从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仍然不清楚。我们现在已经研究了肌动蛋白动力学和成脂诱导之间的机械关系。瞬时暴露于肌动蛋白解聚剂latrunculin A（LatA）支持形成脂肪细胞相关的皮质肌动蛋白结构和完成终端脂肪细胞分化的存在下，胰岛素，而长期暴露于LatA阻止这样的肌动蛋白重组以及终端脂肪形成。此外，胰岛素的这些作用通过抑制磷脂酰肌醇3-激酶（PI 3 K）-Rac 1信号传导和肌动蛋白相关蛋白2/3（Arp 2/3）复合物（其是皮质肌动蛋白网络的关键组分）来防止。因此，我们的研究结果表明，胰岛素-PI 3 K-Rac 1轴导致脂肪细胞相关的皮质肌动蛋白结构的形成，这是完成脂肪细胞分化所必需的。
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.