Journal article
Control of lysosomal biogenesis and Notch-dependent tissue patterning by components of the TFEB-V-ATPase axis in Drosophila melanogaster
FIRC Institute of Molecular Oncology1
Department of Systems Biology, Technical University of Denmark2
Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark3
Regulatory Genomics, Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark4
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.
Language: | English |
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Publisher: | Taylor & Francis |
Year: | 2016 |
Pages: | 499-514 |
ISSN: | 15548635 and 15548627 |
Types: | Journal article |
DOI: | 10.1080/15548627.2015.1134080 |
ORCIDs: | De Masi, Federico |
Autophagy Lysosome Mitf Notch signaling Patterning SOP TFEB V-ATPase
Animals Body Patterning Cell Differentiation Drosophila Proteins Drosophila melanogaster Epithelial Cells Humans Imaginal Discs Lysosomes Models, Biological N protein, Drosophila Neurons Receptors, Notch Sequence Homology, Amino Acid Signal Transduction Transcription, Genetic Vacuolar Proton-Translocating ATPases Wings, Animal autophagy lysosome mitf patterning