Patched regulates lipid

Cadena Del Castillo, Carla E. and Hannich, J. Thomas and Kaech, Andres and Chiyoda, Hirohisa and Brewer, Jonathan and Fukuyama, Masamitsu and Færgeman, Nils J. and Riezman, Howard and Spang, Anne. (2021) Patched regulates lipid. Nature Communications, 12 (1). p. 4898.

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Official URL: https://edoc.unibas.ch/86796/

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Hedgehog (Hh) signaling is essential during development and in organ physiology. In the canonical pathway, Hh binding to Patched (PTCH) relieves the inhibition of Smoothened (SMO). Yet, PTCH may also perform SMO-independent functions. While the PTCH homolog PTC-3 is essential in C. elegans, worms lack SMO, providing an excellent model to probe non-canonical PTCH function. Here, we show that PTC-3 is a cholesterol transporter. ptc-3(RNAi) leads to accumulation of intracellular cholesterol and defects in ER structure and lipid droplet formation. These phenotypes were accompanied by a reduction in acyl chain (FA) length and desaturation. ptc-3(RNAi)-induced lethality, fat content and ER morphology defects were rescued by reducing dietary cholesterol. We provide evidence that cholesterol accumulation modulates the function of nuclear hormone receptors such as of the PPARα homolog NHR-49 and NHR-181, and affects FA composition. Our data uncover a role for PTCH in organelle structure maintenance and fat metabolism.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Growth & Development > Biochemistry (Spang)
UniBasel Contributors:Spang, Anne
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Publishing Group
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:03 Mar 2022 15:40
Deposited On:03 Mar 2022 15:37

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