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Patched regulates Smoothened trafficking using lipoprotein-derived lipids
Helena Khaliullina1, Daniela Panáková, Christina Eugster
1Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse-108, 01307 Dresden, Germany.
Development (Cambridge, England)
|November 13, 2009
Summary
Patched (Ptc) protein uses lipoprotein lipids to degrade Smoothened (Smo) signaling. Hedgehog (Hh) binding to Ptc inhibits this lipid utilization, revealing a novel mechanism for pathway regulation.
Area of Science:
- Cell Biology
- Molecular Biology
- Developmental Biology
Background:
- Hedgehog (Hh) signaling is crucial for tissue patterning and proliferation.
- Patched (Ptc) receptor represses Smoothened (Smo) signaling in the absence of Hh.
- Ptc's sterol-sensing domain suggests a role in lipid regulation, but direct evidence was lacking.
Purpose of the Study:
- To investigate the mechanism by which Patched (Ptc) represses Smoothened (Smo) signaling.
- To determine if Ptc regulates lipid trafficking to control Smo signaling.
- To elucidate the role of lipoproteins and lipids in Hh pathway regulation.
Main Methods:
- Utilized Drosophila as a model organism.
- Investigated the interaction of Ptc with internalized lipoproteins.
- Analyzed the role of Ptc's sterol-sensing domain in lipid and Smo trafficking.
- Examined Smo levels on the basolateral membrane.
Main Results:
- Drosophila Ptc recruits internalized lipoproteins to Ptc-positive endosomes.
- Ptc's sterol-sensing domain controls lipid and Smo trafficking from endosomes.
- Ptc uses lipoprotein-derived lipids to destabilize Smo on the basolateral membrane.
- Hedgehog (Hh) binding to lipoproteins inhibits Ptc's utilization of their lipids.
Conclusions:
- Ptc regulates Smo degradation by altering endosomal lipid composition.
- Lipoprotein lipids are key mediators in Ptc-mediated repression of Smo signaling.
- Hh acts by preventing Ptc from accessing and utilizing lipoprotein lipids.
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