Phospholipid Homeostasis Regulates Dendrite Morphogenesis in Drosophila Sensory Neurons

Abstract

Summary: Disruptions in lipid homeostasis have been observed in many neurodevelopmental disorders that are associated with dendrite morphogenesis defects. However, the molecular mechanisms of how lipid homeostasis affects dendrite morphogenesis are unclear. We find that easily shocked (eas), which encodes a kinase with a critical role in phospholipid phosphatidylethanolamine (PE) synthesis, and two other enzymes in this synthesis pathway are required cell autonomously in sensory neurons for dendrite growth and stability. Furthermore, we show that the level of Sterol Regulatory Element-Binding Protein (SREBP) activity is important for dendrite development. SREBP activity increases in eas mutants, and decreasing the level of SREBP and its transcriptional targets in eas mutants largely suppresses the dendrite growth defects. Furthermore, reducing Ca2+ influx in neurons of eas mutants ameliorates the dendrite morphogenesis defects. Our study uncovers a role for EAS kinase and reveals the in vivo function of phospholipid homeostasis in dendrite morphogenesis. : Meltzer et al. show that EAS, a conserved kinase in the phospholipid phosphatidylethanolamine synthesis pathway, regulates dendrite growth via SREBP signaling and Ca2+ influx. Their study reveals the role of phospholipid homeostasis in dendrite morphogenesis in vivo. Keywords: dendrite, sensory neurons, morphogenesis, Drosophila, phospholipid, homeostasis, lipid