Artículo de revista
Phosphatidic acid increases Notch signalling by affecting Sanpodo trafficking during Drosophila sensory organ development
Fecha
2020Registro en:
Scientific Reports (2020) 10:21731
10.1038/s41598-020-78831-z
Autor
Medina Yáñez, Ignacio
Olivares, Gonzalo H.
Vega Macaya, Franco
Mlodzik, Marek
Olguín, Patricio
Institución
Resumen
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.