Phosphatidic acid increases Notch signalling by affecting Sanpodo trafficking during Drosophila sensory organ development
Author
dc.contributor.author
Medina Yáñez, Ignacio
Author
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Olivares, Gonzalo H.
Author
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Vega Macaya, Franco
Author
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Mlodzik, Marek
Author
dc.contributor.author
Olguín, Patricio
Admission date
dc.date.accessioned
2021-08-23T23:18:36Z
Available date
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2021-08-23T23:18:36Z
Publication date
dc.date.issued
2020
Cita de ítem
dc.identifier.citation
Scientific Reports (2020) 10:21731
es_ES
Identifier
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10.1038/s41598-020-78831-z
Identifier
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https://repositorio.uchile.cl/handle/2250/181424
Abstract
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Organ cell diversity depends on binary cell-fate decisions mediated by the Notch signalling pathway
during development and tissue homeostasis. A clear example is the series of binary cell-fate decisions
that take place during asymmetric cell divisions that give rise to the sensory organs of Drosophila
melanogaster. The regulated trafficking of Sanpodo, a transmembrane protein that potentiates
receptor activity, plays a pivotal role in this process. Membrane lipids can regulate many signalling
pathways by affecting receptor and ligand trafficking. It remains unknown, however, whether
phosphatidic acid regulates Notch-mediated binary cell-fate decisions during asymmetric cell
divisions, and what are the cellular mechanisms involved. Here we show that increased phosphatidic
acid derived from Phospholipase D leads to defects in binary cell-fate decisions that are compatible
with ectopic Notch activation in precursor cells, where it is normally inactive. Null mutants of numb or
the α-subunit of Adaptor Protein complex-2 enhance dominantly this phenotype while removing a copy
of Notch or sanpodo suppresses it. In vivo analyses show that Sanpodo localization decreases at acidic
compartments, associated with increased internalization of Notch. We propose that Phospholipase
D-derived phosphatidic acid promotes ectopic Notch signalling by increasing receptor endocytosis and
inhibiting Sanpodo trafficking towards acidic endosomes.
es_ES
Patrocinador
dc.description.sponsorship
Biomedical Neuroscience Institute, Iniciativa Cientifica Milenio ICM P09-015F