837V Poster - 13. Neural development and physiology
Wednesday April 06, 4:00 PM - 7:00 PM

Authors:
Jun Yin; Hsueh-Ling Cheng; Jingce Lei; Anna Grigsby-Brown; Mary Gibbs; Aidan Dermady; Quan Yun

Affiliation: National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD

Keywords:
k. glia; g. oxidative damage

Lipid trafficking between neurons and glia contributes to the development, function, and stress responses of the nervous system. Due to the diversity of lipid transport proteins and lipoprotein receptors, cellular and molecular pathways involved in neuron-glia lipid shuttling have not been well characterized in vivo under physiological conditions. How neurons obtain their lipid supply during development and how synaptic activity regulates this process remain open questions. To identify the molecular network involved in this process, we performed genetic screens on glia-derived secretory factors and evaluated their distributions and functions in the Drosophila central nervous system (CNS). One of our top hits is Odorant-Binding-Protein 44a (Obp44a), a small secretory protein highly expressed in both larval and adult astrocytes. Structure homology modeling indicates OBP44a as a lipid binding protein that potentially interacts with both fatty acids and cholesterol. Using CRISPR-medicated genome editing, we generated knock-in and knock-out OBP44a alleles, validated its glial expression and revealed its specific functions in regulating the physiological properties of fly neurons. Notably, OBP44a level is upregulated in flies challenged with the H2O2 treatment, while the mutant shows a significant reduction in their resistance to oxidative stress, as well as deficits in locomotor activity and sleep maintenance. Based on these findings, we propose that Obp44a functions as an antioxidant that protects lipids from peroxidation within the fly brain and represents a new class of glia-derived molecules contributing to the unique CNS lipid environment.