The interplay of Patched, Smoothened and cholesterol in Hedgehog signaling

Current Opinion in Cell Biology
Ao Hu, Bao-Liang Song

Abstract

The Hedgehog (HH) pathway plays a pivotal role in regulating a diverse array of events from embryonic tissue patterning to adult organ self-renewal. Aberrant activation of the pathway is linked to carcinogenesis. Key factors in the HH pathway include the signaling ligand HH, the receptor Patched (PTCH), and the G-protein-coupled receptor-like transducer Smoothened (SMO). A long-lasting question about this pathway is how PTCH prevents SMO from being activated. Recent high-resolution structural studies provide insight into the molecular basis of HH recognition by PTCH. Moreover, cholesterol stands out as the endogenous ligand of SMO and acts by binding and/or covalently linking to SMO. In this review, we discuss current advances in HH signaling, the interplay of PTCH, SMO and cholesterol, and propose putative models of SMO activation by cholesterol binding and/or modification.

Citations

Jan 8, 2020·Journal of Lipid Research·Mustafa YalcinkayaArnold von Eckardstein
Sep 16, 2020·Traffic·Yvonne Lange, Theodore L Steck
Mar 20, 2020·Physiological Reviews·Marianela G DalghiGerard Apodaca
Jul 11, 2020·Life Science Alliance·Hongwen ChenXiaochun Li
Sep 16, 2020·Nature Chemical Biology·Xiaofeng QiXiaochun Li
Jan 10, 2021·Science China. Life Sciences·Jie LuoBao-Liang Song
Feb 2, 2021·Frontiers in Neural Circuits·G Giacomo ConsalezRichard Hawkes
Dec 23, 2020·Journal of Neuroscience Research·Gina La SalaGlauco P Tocchini-Valentini
Apr 6, 2021·World Journal of Hepatology·Yana V KiselevaYuri O Zharikov
Jun 22, 2021·Annual Review of Biochemistry·Marc M Schumacher, Russell A DeBose-Boyd
Aug 28, 2021·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Zhi-Ping QiuBao-Liang Song

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