title: Control of lysosomal biogenesis and Notch-dependent tissue patterning by components of the TFEB-V-ATPase axis in Drosophila melanogaster.
abstract: In vertebrates, TFEB (transcription factor EB) and MITF (microphthalmia-associated transcription factor) family of basic Helix-Loop-Helix (bHLH) transcription factors regulates both lysosomal function and organ development. However, it is not clear whether these 2 processes are interconnected. Here, we show that Mitf, the single TFEB and MITF ortholog in Drosophila, controls expression of vacuolar-type H(+)-ATPase pump (V-ATPase) subunits. Remarkably, we also find that expression of Vha16-1 and Vha13, encoding 2 key components of V-ATPase, is patterned in the wing imaginal disc. In particular, Vha16-1 expression follows differentiation of proneural regions of the disc. These regions, which will form sensory organs in the adult, appear to possess a distinctive endolysosomal compartment and Notch (N) localization. Modulation of Mitf activity in the disc in vivo alters endolysosomal function and disrupts proneural patterning. Similar to our findings in Drosophila, in human breast epithelial cells we observe that impairment of the Vha16-1 human ortholog ATP6V0C changes the size and function of the endolysosomal compartment and that depletion of TFEB reduces ligand-independent N signaling activity. Our data suggest that lysosomal-associated functions regulated by the TFEB-V-ATPase axis might play a conserved role in shaping cell fate.
authors.affiliation: a IFOM - FIRC Institute of Molecular Oncology , Milan , Italy.
authors.forename: Emiliana
authors.initials: E
authors.lastname: Tognon
authors.affiliation: a IFOM - FIRC Institute of Molecular Oncology , Milan , Italy.
authors.forename: Francis
authors.initials: F
authors.lastname: Kobia
authors.affiliation: a IFOM - FIRC Institute of Molecular Oncology , Milan , Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Busi
authors.affiliation: a IFOM - FIRC Institute of Molecular Oncology , Milan , Italy.
authors.forename: Arianna
authors.initials: A
authors.lastname: Fumagalli
authors.affiliation: b Center for Biological Sequence Analysis, Institute for Systems Biology, Technical University of Denmark , Lyngby , Denmark.
authors.forename: Federico
authors.initials: F
authors.lastname: De Masi
authors.affiliation: a IFOM - FIRC Institute of Molecular Oncology , Milan , Italy.
authors.forename: Thomas
authors.initials: T
authors.lastname: Vaccari
mesh_terms: D000818:Animals; D019521:Body Patterning; D002454:Cell Differentiation; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D060227:Imaginal Discs / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism*; D008954:Models, Biological; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014158:Transcription, Genetic; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics / Q000378:metabolism*; D014921:Wings, Animal / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; C497759:N protein, Drosophila; D051880:Receptors, Notch; D025262:Vacuolar Proton-Translocating ATPases
keywords: Notch signaling; SOP; TFEB; V-ATPase; autophagy; lysosome; mitf; patterning