Macroautophagy supports Sonic Hedgehog signaling by promoting Patched1 degradation
Macroautophagy supports Sonic Hedgehog signaling by promoting Patched1 degradation
复制标题
巨自噬通过促进 Patched1 降解来支持 Sonic Hedgehog 信号传导
DOI：
10.1016/j.bbamcr.2021.119124
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发表时间：
2021-08-28
影响因子：
5.1
通讯作者：
Yue, Shen
中科院分区：
文献类型：
--
作者：
Yang, Xin;Jin, Nan;Yue, Shen
自噬是一种高度保守的自我消化过程，用于维持细胞内稳态并确保细胞在压力下生存。 Sonic Hedgehog (Shh) 信号传导的激活取决于通路受体 Patched1 (Ptch1) 的正常内吞降解。目前尚不清楚自噬是否参与受体内吞作用并调节 Shh 信号转导。在这里，我们发现，由于 Smoothened (Smo) 未能转运到初级纤毛中，阻断巨自噬会减弱 Shh 信号传导。在 Smo 的上游，Ptch1 通过 K63 缀合的泛素链被多泛素化。巨自噬参与 Shh 诱导的多泛素化 Ptch1 降解，有助于激活 Shh 信号传导。
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.