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 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.

Genome‐wide identification, classification, and expression profiling of serine esterases and other esterase‐related proteins in the tobacco hornworm, Manduca sexta

“…, 2009; Stanley & Kim, 2019; Medina‐Yáñez et al. , 2020). It is pleasing that the 183 important genes from four different groups have been annotated at a high quality, in terms of model accuracy, richness of structural information, and spatiotemporal expression patterns of mRNA and some proteins.…”

“…The selection of lipases, carboxylesterases, and thioesterases stemmed from our general interests in lipid metabolism in M. sexta. We also explored phospholipase-like proteins, because some of them (e.g., PLA 2 s, PLCs, and PLDs) may play roles in cell signaling during immune responses or development (Ha et al, 2009;Stanley & Kim, 2019;Medina-Yáñez et al, 2020). It is pleasing that the 183 important genes from four different groups have been annotated at a high quality, in terms of model accuracy, richness of structural information, and spatiotemporal expression patterns of mRNA and some proteins.…”

Early-life nutrition interacts with developmental genes to shape the brain and sleep behavior inDrosophila melanogaster

“…The flies were placed on Sylgard plates with 70% ethanol, legs and wings were removed avoiding damage. After immobilizing the sample, the ILUMINA software was used to take a picture of the head and thoraxes at 6X with a stereoscopic magnifier attached to an INFINITY Lumenal Photo Camera 1 88 . All images were processed and assembled using Fiji software and Adobe Illustrator 2020.…”

Phosphatidic acid: from biophysical properties to diverse functions

“…In Drosophila, PLD activity couples endocytosis of Rhodopsin 1 loaded vesicles with their recycling to the plasma membrane, thus maintaining plasma membrane composition and size [3]. PLD-derived PA promotes ectopic Notch signalling by increasing receptor endocytosis and inhibiting Sanpodo trafficking towards acidic endosomes [29]. Finally, the PLD inhibitor FIPI reduced compensatory endocytosis of secretory granule membrane turnover [25,30].…”