Phospholipid Homeostasis Regulates Dendrite Morphogenesis in Drosophila Sensory Neurons
Shan Meltzer,
Joshua A. Bagley,
Gerardo Lopez Perez,
Caitlin E. O’Brien,
Laura DeVault,
Yanmeng Guo,
Lily Yeh Jan,
Yuh-Nung Jan
Affiliations
Shan Meltzer
Howard Hughes Medical Institute, Departments of Physiology, Biochemistry, and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA
Joshua A. Bagley
Howard Hughes Medical Institute, Departments of Physiology, Biochemistry, and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA
Gerardo Lopez Perez
Howard Hughes Medical Institute, Departments of Physiology, Biochemistry, and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA
Caitlin E. O’Brien
Howard Hughes Medical Institute, Departments of Physiology, Biochemistry, and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA
Laura DeVault
Howard Hughes Medical Institute, Departments of Physiology, Biochemistry, and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA
Yanmeng Guo
Howard Hughes Medical Institute, Departments of Physiology, Biochemistry, and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA
Lily Yeh Jan
Howard Hughes Medical Institute, Departments of Physiology, Biochemistry, and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA
Yuh-Nung Jan
Howard Hughes Medical Institute, Departments of Physiology, Biochemistry, and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA; Corresponding author
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
