Phosphatidic acid increases Notch signalling by affecting Sanpodo trafficking during Drosophila sensory organ development

Abstract 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...

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Autores principales: Ignacio Medina-Yáñez, Gonzalo H. Olivares, Franco Vega-Macaya, Marek Mlodzik, Patricio Olguín
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Publicado: Nature Portfolio 2020
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Acceso en línea:https://doaj.org/article/f18663aa686d425ca097bcd249292927
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spelling oai:doaj.org-article:f18663aa686d425ca097bcd2492929272021-12-02T12:33:04ZPhosphatidic acid increases Notch signalling by affecting Sanpodo trafficking during Drosophila sensory organ development10.1038/s41598-020-78831-z2045-2322https://doaj.org/article/f18663aa686d425ca097bcd2492929272020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78831-zhttps://doaj.org/toc/2045-2322Abstract 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.Ignacio Medina-YáñezGonzalo H. OlivaresFranco Vega-MacayaMarek MlodzikPatricio OlguínNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-12 (2020)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Ignacio Medina-Yáñez
Gonzalo H. Olivares
Franco Vega-Macaya
Marek Mlodzik
Patricio Olguín
Phosphatidic acid increases Notch signalling by affecting Sanpodo trafficking during Drosophila sensory organ development
description Abstract 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.
format article
author Ignacio Medina-Yáñez
Gonzalo H. Olivares
Franco Vega-Macaya
Marek Mlodzik
Patricio Olguín
author_facet Ignacio Medina-Yáñez
Gonzalo H. Olivares
Franco Vega-Macaya
Marek Mlodzik
Patricio Olguín
author_sort Ignacio Medina-Yáñez
title Phosphatidic acid increases Notch signalling by affecting Sanpodo trafficking during Drosophila sensory organ development
title_short Phosphatidic acid increases Notch signalling by affecting Sanpodo trafficking during Drosophila sensory organ development
title_full Phosphatidic acid increases Notch signalling by affecting Sanpodo trafficking during Drosophila sensory organ development
title_fullStr Phosphatidic acid increases Notch signalling by affecting Sanpodo trafficking during Drosophila sensory organ development
title_full_unstemmed Phosphatidic acid increases Notch signalling by affecting Sanpodo trafficking during Drosophila sensory organ development
title_sort phosphatidic acid increases notch signalling by affecting sanpodo trafficking during drosophila sensory organ development
publisher Nature Portfolio
publishDate 2020
url https://doaj.org/article/f18663aa686d425ca097bcd249292927
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