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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2020
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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) |
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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 |
work_keys_str_mv |
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