Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France; Centre National de la Recherche Scientifique, UMR7104, Illkirch, France; Institut National de la Santé et de la Recherche Médicale, U964, Illkirch, France; Université de Strasbourg, Illkirch, France.
Imagine-Institut Pasteur, Laboratory of Heart Morphogenesis, Paris, France; INSERM UMR1163, Université Paris Descartes, Paris, France; Sorbonne Université, Collège Doctoral, F-75005, Paris, France.
Cell Rep. 2020 Jul 21;32(3):107932. doi: 10.1016/j.celrep.2020.107932.
Cilia and the intraflagellar transport (IFT) proteins involved in ciliogenesis are associated with congenital heart diseases (CHDs). However, the molecular links between cilia, IFT proteins, and cardiogenesis are yet to be established. Using a combination of biochemistry, genetics, and live-imaging methods, we show that IFT complex B proteins (Ift88, Ift54, and Ift20) modulate the Hippo pathway effector YAP1 in zebrafish and mouse. We demonstrate that this interaction is key to restrict the formation of the proepicardium and the myocardium. In cellulo experiments suggest that IFT88 and IFT20 interact with YAP1 in the cytoplasm and functionally modulate its activity, identifying a molecular link between cilia-related proteins and the Hippo pathway. Taken together, our results highlight a noncanonical role for IFT complex B proteins during cardiogenesis and shed light on a mechanism of action for ciliary proteins in YAP1 regulation.
纤毛和参与纤毛发生的内鞭毛运输（IFT）蛋白与先天性心脏病（CHD）有关。然而，纤毛、IFT 蛋白和心脏发生之间的分子联系尚待确定。我们使用生物化学、遗传学和活体成像方法的组合，表明 IFT 复合物 B 蛋白（Ift88、Ift54 和 Ift20）在斑马鱼和小鼠中调节 Hippo 通路效应物 YAP1。我们证明这种相互作用对于限制前肠和心肌的形成至关重要。细胞内实验表明，IFT88 和 IFT20 在细胞质中与 YAP1 相互作用，并在功能上调节其活性，从而确定了与纤毛相关蛋白和 Hippo 通路之间的分子联系。总之，我们的研究结果强调了 IFT 复合物 B 蛋白在心脏发生过程中的非典型作用，并阐明了纤毛蛋白在 YAP1 调节中的作用机制。
