Macroautophagy supports Sonic Hedgehog signaling by promoting Patched1 degradation |
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| Institution: | 1. Department of Medical Genetics, Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing 211166, China;2. The First School of Clinical Medicine, Nanjing Medical University, Nanjing 211166, China;3. Department of Pathology, Suzhou Ninth People''s Hospital, Suzhou 215200, PR China;4. Key Laboratory of Women''s Reproductive Health of Jiangxi, Jiangxi Maternal & Child Health Hospital, Nanchang, Jiangxi 330006, PR China;5. Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211166, China |
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| Abstract: | 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. |
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