磷脂稳态调控果蝇感觉神经元树突形态发生。
Phospholipid Homeostasis Regulates Dendrite Morphogenesis in Drosophila Sensory Neurons.
机构信息
Howard Hughes Medical Institute, Departments of Physiology, Biochemistry, and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
Howard Hughes Medical Institute, Departments of Physiology, Biochemistry, and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
出版信息
Cell Rep. 2017 Oct 24;21(4):859-866. doi: 10.1016/j.celrep.2017.09.089.
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 Ca 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.
脂质稳态的紊乱在许多与树突形态发生缺陷相关的神经发育障碍中都有观察到。然而，脂质稳态如何影响树突形态发生的分子机制尚不清楚。我们发现，编码一种在磷脂磷脂酰乙醇胺（PE）合成中起关键作用的激酶的 eas 基因，以及该合成途径中的另外两种酶，在感觉神经元中自主地需要细胞来维持树突的生长和稳定性。此外，我们还表明固醇调节元件结合蛋白（SREBP）活性的水平对树突的发育很重要。 eas 突变体中的 SREBP 活性增加，降低 eas 突变体中 SREBP 及其转录靶标的水平在很大程度上抑制了树突生长缺陷。此外，减少 eas 突变体神经元中的 Ca 流入可改善树突形态发生缺陷。我们的研究揭示了 EAS 激酶的作用，并揭示了磷脂稳态在树突形态发生中的体内功能。
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