In response to stress conditions, autophagy activity in multicellular organisms is systemically modulated to ensure maintenance of cellular homeostasis at an organismal level. Very little is known about the intercellular signals that elicit the long-range organism-wide autophagy response. Here we showed that during Caenorhabditis elegans development, loss of cuticle annular furrow collagens elicits autophagy in the hypodermis, intestine, and muscle. The cilia of sensory neurons with cuticle-localized endings are essential for triggering this systemic response. The TGFβ-like molecule DAF-7, which is secreted in part from a specific pair of ciliated neurons, acts as a systemic factor that activates a canonical TGFβ signaling pathway in distant tissues to induce autophagy. We also showed that AAK-2/AMPK and the STAT-like protein STA-2 act differentially in different tissues for autophagy activation. Our study reveals a circuit that senses and transduces the signal from the damaged cuticle to activate systemic autophagy during animal development.

中文翻译：

---

TGFβ 样 DAF-7 充当线虫自噬调节的系统信号

为了应对应激条件，多细胞生物体中的自噬活性受到系统调节，以确保在生物体水平上维持细胞稳态。对于引起生物体范围内的长程自噬反应的细胞间信号知之甚少。在这里，我们发现，在秀丽隐杆线虫发育过程中，角质层环形沟胶原蛋白的丧失会引起皮下组织、肠道和肌肉的自噬。具有角质层局部末端的感觉神经元的纤毛对于触发这种全身反应至关重要。TGFβ 样分子 DAF-7 部分由一对特定的纤毛神经元分泌，作为系统因子激活远处组织中的典型 TGFβ 信号通路以诱导自噬。我们还表明，AAK-2/AMPK 和 STAT 样蛋白 STA-2 在不同组织中对自噬激活的作用存在差异。我们的研究揭示了一个在动物发育过程中感知和转换来自受损角质层的信号以激活系统自噬的电路。