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          Institute: MPI für molekulare Zellbiologie und Genetik     Collection: MPI-CBG Publications 2015 (arch)     Display Documents



ID: 718058.0, MPI für molekulare Zellbiologie und Genetik / MPI-CBG Publications 2015 (arch)
Endocannabinoids are conserved inhibitors of the Hedgehog pathway.
Authors:Khaliullina, Helena; Bilgin, Mesut; Sampaio, Julio; Shevchenko, Andrej; Eaton, Suzanne
Date of Publication (YYYY-MM-DD):2015
Title of Journal:Proceedings of the National Academy of Sciences of the United States of America
Volume:112
Issue / Number:11
Start Page:3415
End Page:3420
Copyright:not available
Audience:Experts Only
Intended Educational Use:No
Abstract / Description:Hedgehog ligands control tissue development and homeostasis by alleviating repression of Smoothened, a seven-pass transmembrane protein. The Hedgehog receptor, Patched, is thought to regulate the availability of small lipophilic Smoothened repressors whose identity is unknown. Lipoproteins contain lipids required to repress Smoothened signaling in vivo. Here, using biochemical fractionation and lipid mass spectrometry, we identify these repressors as endocannabinoids. Endocannabinoids circulate in human and Drosophila lipoproteins and act directly on Smoothened at physiological concentrations to repress signaling in Drosophila and mammalian assays. Phytocannabinoids are also potent Smo inhibitors. These findings link organismal metabolism to local Hedgehog signaling and suggest previously unsuspected mechanisms for the physiological activities of cannabinoids.
External Publication Status:published
Document Type:Article
Communicated by:Thüm
Affiliations:MPI für molekulare Zellbiologie und Genetik
Identifiers:LOCALID:6141
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