title: The Hedgehog signalling pathway regulates autophagy.
abstract: Autophagy is a highly conserved degradative process that removes damaged or unnecessary proteins and organelles, and recycles cytoplasmic contents during starvation. Autophagy is essential in physiological processes such as embryonic development but how autophagy is regulated by canonical developmental pathways is unclear. Here we show that the Hedgehog signalling pathway inhibits autophagosome synthesis, both in basal and in autophagy-induced conditions. This mechanism is conserved in mammalian cells and in Drosophila, and requires the orthologous transcription factors Gli2 and Ci, respectively. Furthermore, we identify that activation of the Hedgehog pathway reduces PERK levels, concomitant with a decrease in phosphorylation of the translation initiation factor eukaryotic initiation factor 2α, suggesting a novel target of this pathway and providing a possible link between Hedgehog signalling and autophagy.
authors.affiliation: Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0XY, UK.
authors.forename: Maria
authors.initials: M
authors.lastname: Jimenez-Sanchez
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Menzies
authors.forename: Yu-Yun
authors.initials: YY
authors.lastname: Chang
authors.forename: Nikol
authors.initials: N
authors.lastname: Simecek
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Neufeld
authors.forename: David C
authors.initials: DC
authors.lastname: Rubinsztein
mesh_terms: D000818:Animals; D001343:Autophagy; D015536:Down-Regulation; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology / Q000378:metabolism; D005216:Fat Body / Q000166:cytology / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D053823:Hedgehog Proteins / Q000819:agonists / Q000378:metabolism*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D051379:Mice; D000072079:Patched Receptors; D010588:Phagosomes / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic; D000075746:Zinc Finger Protein Gli2; D019892:eIF-2 Kinase
chemical_list: D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D000072079:Patched Receptors; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D000075746:Zinc Finger Protein Gli2; D019892:eIF-2 Kinase; C000618551:Gli2 protein, mouse