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07:26
Quantitative PCR-based Assay to Measure Sonic Hedgehog Signaling in Cellular Model of Ciliogenesis
Published on: January 31, 2025
817
Cholesterol access in cellular membranes controls Hedgehog signaling
Arun Radhakrishnan1, Rajat Rohatgi2, Christian Siebold3
1Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX, USA. arun.radhakrishnan@utsouthwestern.edu.
Nature Chemical Biology
|November 17, 2020
Summary
Accessible cholesterol acts as a second messenger in the Hedgehog (Hh) signaling pathway, mediating communication between Patched 1 (PTCH1) and Smoothened (SMO) proteins. This finding reveals new insights into membrane biology and Hh pathway regulation.
Area of Science:
- Membrane Biology
- Cell Signaling
- Developmental Biology
Background:
- The Hedgehog (Hh) signaling pathway is crucial for development and regeneration.
- Dysregulation of Hh signaling is implicated in various diseases, including birth defects and cancer.
- Hh signal transmission across the plasma membrane involves Patched 1 (PTCH1) and Smoothened (SMO) proteins.
Purpose of the Study:
- To elucidate the mechanism of Hh signal transduction across the plasma membrane.
- To investigate the role of cholesterol in Hh pathway signaling.
- To uncover novel principles in membrane biology related to cholesterol-protein interactions.
Main Methods:
- Structural biology techniques
- Biochemical assays
- Cell-based biological studies
Main Results:
- A specific pool of plasma membrane cholesterol, termed accessible cholesterol, acts as a second messenger.
- Accessible cholesterol facilitates signal transfer between PTCH1 and SMO.
- Demonstrated how proteins remodel cholesterol accessibility and how organelle membrane cholesterol regulates protein function.
Conclusions:
- Accessible cholesterol is a key component in Hh signal transmission.
- These findings offer new perspectives on membrane cholesterol's role in cellular signaling.
- The study highlights the intricate relationship between membrane lipid composition and protein function.
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