9.B.421. The Sanpodo (Spdo) Family

Sanpodo in D. melanogaster is involved in assymetic cell division and heart morphogenesis. It is a regulator of the Notch signaling pathway and plays a role in peripheral nervous system development including sensory nerve development. The regulated trafficking of Sanpodo, which potentiates receptor activity, plays a role in these processes. Medina-Yáñez et al. 2020 showed that increased phosphatidic acid, derived from phospholipase D action, 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 in numb (TC# 8.A.87.3.1) or the alpha-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 in acidic compartments, associated with increased internalization of Notch. Medina-Yáñez et al. 2020 proposed that phospholipase D-derived phosphatidic acid promotes ectopic Notch signalling by increasing receptor endocytosis and inhibiting Sanpodo trafficking towards acidic endosomes.