Primary cilium-dependent macroautophagy/autophagy is induced by the urinary flow in epithelial cells of the kidney proximal tubule. A major physiological outcome of this cascade is the control of cell size. Some components of the ATG machinery are recruited at the primary cilium to generate autophagic structures. Shear stress induced by the liquid flow promotes PtdIns3P synthesis at the primary cilium, and this lipid is required both for ciliogenesis and initiation of autophagy. We showed that PtdIns3P is generated by PIK3C2A, but not by PIK3C3/VPS34, during flow-associated primary cilium-dependent autophagy, in a ULK1-independent manner. Along the same line BECN1 (beclin 1), a partner of PIK3C3 in starvation-induced autophagy, is not recruited at the primary cilium under shear stress. Thus, kidney epithelial cells mobilize different PtdIns 3-kinases, i.e., PIK3C2A or PIK3C3, to produce PtdIns3P in order to initiate autophagy depending on the stimuli (shear stress or starvation). ABBREVIATIONS PtdIns3P: phosphatidylinositol-3-phosphate; PIK3C2A: class two alpha phosphatidylinositol 3-kinase; PIK3C3/VPS34: class three phosphatidylinositol 3-kinase; ATG: autophagy associated genes.

中文翻译：

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主要的依赖纤毛的自噬起草PIK3C2A以响应剪切应力生成PtdIns3P。

肾近端小管上皮细胞中的尿流诱导原发性纤毛依赖性自噬/自噬。该级联反应的主要生理结果是细胞大小的控制。ATG机械的某些组件在初级纤毛上募集，以产生自噬结构。液流引起的剪切应力促进初级纤毛上PtdIns3P的合成，而这种脂质对于纤毛的形成和自噬的启动都是必需的。我们显示PtdIns3P是由PIK3C2A生成的，而不是由PIK3C3 / VPS34生成的，在与流程相关的主要纤毛依赖性自噬过程中，以ULK1无关的方式产生。沿着相同的路线，BECN1（beclin 1）是PIK3C3在饥饿诱导自噬中的伴侣，在剪切应力下不会在初级纤毛上募集。从而，肾脏上皮细胞动员不同的PtdIns 3激酶（即PIK3C2A或PIK3C3）产生PtdIns3P，以便根据刺激（剪切应力或饥饿）启动自噬。缩写PtdIns3P：磷脂酰肌醇-3-磷酸; PIK3C2A：第二类α磷脂酰肌醇3-激酶；PIK3C3 / VPS34：三类磷脂酰肌醇3-激酶；ATG：自噬相关基因。