Autophagy is a highly conservative self-digestion process to maintain intracellular homeostasis and to ensure the survival of cells under stress. Activation of Sonic Hedgehog (Shh) signaling depends on the normal endocytic degradation of pathway receptor Patched1 (Ptch1). It is unclear whether autophagy participates in the receptor endocytosis and modulates Shh signaling transduction. Here we found that blocking macroautophagy attenuates Shh signaling due to the failed transport of Smoothened (Smo) into primary cilia. At the upstream of Smo, Ptch1 was poly-ubiquitinated through K63-conjugated ubiquitin chains. Macroautophagy participates Shh-induced degradation of poly-ubiquitinated Ptch1, contributing to the activation of Shh signaling.

自噬是一种高度保守的自我消化过程，以维持细胞内稳态并确保细胞在压力下的存活。Sonic Hedgehog (Shh) 信号的激活取决于通路受体 Patched1 (Ptch1) 的正常内吞降解。自噬是否参与受体内吞作用并调节 Shh 信号转导尚不清楚。在这里，我们发现由于平滑 (Smo) 到初级纤毛的运输失败，阻断巨自噬减弱了 Shh 信号传导。在 Smo 的上游，Ptch1 通过 K63 共轭泛素链被多泛素化。巨自噬参与 Shh 诱导的多泛素化 Ptch1 降解，有助于激活 Shh 信号。