Phosphatidic acid increases Notch signalling by affecting Sanpodo trafficking during Drosophila sensory organ development.
Sci Rep
; 10(1): 21731, 2020 12 10.
Article
in En
| MEDLINE
| ID: mdl-33303974
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.
Full text:
1
Database:
MEDLINE
Main subject:
Phosphatidic Acids
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Signal Transduction
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Protein Transport
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Drosophila Proteins
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Organogenesis
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Drosophila
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Receptors, Notch
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Mechanoreceptors
Limits:
Animals
Language:
En
Journal:
Sci Rep
Year:
2020
Type:
Article
Affiliation country:
Chile