Zemirli Naïma, Boukhalfa Asma, Dupont Nicolas, Botti Joëlle, Codogno Patrice, Morel Etienne
Institut Necker-Enfants Malades (INEM), INSERM U1151-CNRS UMR 8253.
Université Paris Descartes-Sorbonne Paris Cité, F-75993, Paris, France.
Cell Stress. 2019 Feb 25;3(3):100-109. doi: 10.15698/cst2019.03.180.
Autophagy is a conserved molecular pathway directly involved in the degradation and recycling of intracellular components. Autophagy is associated with a response to stress situations, such as nutrients deficit, chemical toxicity, mechanical stress or microbial host defense. We have recently shown that primary cilium-dependent autophagy is important to control kidney epithelial cell size in response to fluid flow induced shear stress. Here we show that the ciliary protein folliculin (FLCN) actively participates to the signaling cascade leading to the stimulation of fluid flow-dependent autophagy upstream of the cell size regulation in HK2 kidney epithelial cells. The knockdown of FLCN induces a shortening of the primary cilium, inhibits the activation of AMPK and the recruitment of the autophagy protein ATG16L1 at the primary cilium. Altogether, our results suggest that FLCN is essential in the dialog between autophagy and the primary cilium in epithelial cells to integrate shear stress-dependent signaling.
自噬是一种保守的分子途径，直接参与细胞内成分的降解和循环利用。自噬与对应激情况的反应有关，如营养物质缺乏、化学毒性、机械应激或微生物宿主防御。我们最近发现，初级纤毛依赖性自噬对于响应流体流动诱导的剪切应力来控制肾上皮细胞大小很重要。在此我们表明，纤毛蛋白卵泡抑素（FLCN）积极参与信号级联反应，在HK2肾上皮细胞的细胞大小调节上游促进流体流动依赖性自噬。FLCN的敲低导致初级纤毛缩短，抑制AMPK的激活以及自噬蛋白ATG16L1在初级纤毛处的募集。总之，我们的结果表明，FLCN在上皮细胞自噬与初级纤毛之间的对话中至关重要，以整合剪切应力依赖性信号传导。
