Diaphanous regulates myosin and adherens junctions to control cell contractility and protrusive behavior during morphogenesis
Diaphanous regulates myosin and adherens junctions to control cell contractility and protrusive behavior during morphogenesis
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DOI：
10.1242/dev.016337
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发表时间：
2008-03-15
期刊：
影响因子：
4.6
通讯作者：
Peifer, Mark
中科院分区：
文献类型：
--
作者：
Homem, Catarina C. F.;Peifer, Mark
Formins是肌动蛋白成核和伸长的关键调节因子。透明相关福尔马林是最广为人知的亚类，被Rho激活，并在胞质分裂中发挥重要作用。在培养的细胞中，透明相关的福尔马林还调节细胞的黏附、极性和微管，这表明它们可能是发育过程中细胞形状变化和迁移的关键调节因素。然而，它们在胞质分裂中的重要作用阻碍了我们检验这一假说的能力。我们使用功能丧失和功能获得的方法来研究透明蛋白在果蝇形态发生中的作用。我们发现Diaphanous有一种动态的表达模式，与调节细胞形状变化的作用一致。我们使用结构活性透明膜来研究其在形态发生中的作用及其作用机制。这揭示了在细胞形状改变过程中，肌球蛋白在粘连连接处的水平和活性中起到了意想不到的作用，这表明透明肌球蛋白有助于协调潜在的肌球蛋白环的粘连和收缩。我们通过降低透明功能来验证这一假说，揭示了在稳定黏附连接和抑制细胞突起方面的显著作用。这些作用也是通过对肌球蛋白活性和粘附性的协同作用来调节的，这表明了形态发生过程中透明作用的共同机制。
Formins are key regulators of actin nucleation and elongation. Diaphanous-related formins, the best-known subclass, are activated by Rho and play essential roles in cytokinesis. In cultured cells, Diaphanous-related formins also regulate cell adhesion, polarity and microtubules, suggesting that they may be key regulators of cell shape change and migration during development. However, their essential roles in cytokinesis hamper our ability to test this hypothesis. We used loss- and gain-of-function approaches to examine the role of Diaphanous in Drosophila morphogenesis. We found that Diaphanous has a dynamic expression pattern consistent with a role in regulating cell shape change. We used constitutively active Diaphanous to examine its roles in morphogenesis and its mechanisms of action. This revealed an unexpected role in regulating myosin levels and activity at adherens junctions during cell shape change, suggesting that Diaphanous helps coordinate adhesion and contractility of the underlying actomyosin ring. We tested this hypothesis by reducing Diaphanous function, revealing striking roles in stabilizing adherens junctions and inhibiting cell protrusiveness. These effects also are mediated through coordinated effects on myosin activity and adhesion, suggesting a common mechanism for Diaphanous action during morphogenesis.