Control of lysosomal biogenesis and Notch-dependent tissue patterning by components of the TFEB-V-ATPase axis in Drosophila melanogaster

Emiliana Tognon, Francis Kobia, Ilaria Busi, Arianna Fumagalli, Federico De Masi, Thomas Vaccari

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    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, that will form sensory organs in the adult, appear to possess a distinctive endo-lysosomal compartment and Notch (N) localization. Modulation of Mitf activity in the disc in vivo alters endo-lysosomal 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 endo-lysosomal 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.
    Original languageEnglish
    JournalAutophagy
    Volume12
    Issue number3
    Pages (from-to)499-514
    Number of pages16
    ISSN1554-8627
    DOIs
    Publication statusPublished - 2016

    Bibliographical note

    © Emiliana Tognon, Francis Kobia, Ilaria Busi, Arianna Fumagalli, Federico De Masi, and Thomas Vaccari. Published with license by Taylor & Francis. This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.

    Keywords

    • Autophagy
    • Lysosome
    • Mitf
    • Notch signaling
    • Patterning
    • SOP
    • TFEB
    • V-ATPase

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