Glia-derived secretory fatty acid binding protein Obp44a regulates lipid storage and efflux in the developing Drosophila brain.
Glia-derived secretory fatty acid binding protein Obp44a regulates lipid storage and efflux in the developing Drosophila brain.
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胶质细胞衍生的分泌性脂肪酸结合蛋白 Obp44a 调节发育中的果蝇大脑中的脂质储存和流出。
DOI：
10.1101/2024.04.10.588417
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发表时间：
2024
期刊：
影响因子：
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通讯作者：
Zh
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作者：
Yin,Jun;Chen,Hsueh-Ling;Grigsby-Brown,Anna;He,Yi;Cotten,MyriamL;Short,Jacob;Dermady,Aidan;Lei,Jingce;Gibbs,Mary;Cheng,EthanS;Zhang,Dean;Long,Caixia;Xu,Lele;Zhong,Tiffany;Abzalimov,Rinat;Haider,Mariam;Sun,Rong;He,Ye;Zh
胶质细胞来源的分泌因子在支持中枢神经系统(CNS)的发育、生理和应激反应方面发挥着不同的作用。通过转录和图像分析，我们已经确定Obp44a是果蝇中枢神经胶质细胞中产量最高的分泌蛋白之一。蛋白质结构同源性模拟和核磁共振实验表明，Obp44a是一种脂肪酸结合蛋白(FABP)，对天然和氧化形式的长链脂肪酸都有很高的亲和力。进一步的分析表明，Obp44a有效地渗透到神经纤维，在神经元和神经胶质细胞之间传递，并分泌到血淋巴中，作为脂质伴侣和清道夫，在发育中的大脑中调节脂质和氧化还原动态平衡。与这一重要作用相一致的是，Obp44a的缺乏会导致成年动物的解剖和行为缺陷，并导致氧化脂质水平升高。总而言之，我们的发现揭示了维持健康的脑脂环境所需的非规范脂质伴侣在大脑内外运送脂肪酸的关键参与。这些发现可能会启发设计新的方法来恢复中枢神经系统疾病中失调的脂平衡。
Glia derived secretory factors play diverse roles in supporting the development, physiology, and stress responses of the central nervous system (CNS). Through transcriptomics and imaging analyses, we have identified Obp44a as one of the most abundantly produced secretory proteins from Drosophila CNS glia. Protein structure homology modeling and Nuclear Magnetic Resonance (NMR) experiments reveal Obp44a as a fatty acid binding protein (FABP) with a high affinity towards long-chain fatty acids in both native and oxidized forms. Further analyses demonstrate that Obp44a effectively infiltrates the neuropil, traffics between neuron and glia, and is secreted into hemolymph, acting as a lipid chaperone and scavenger to regulate lipid and redox homeostasis in the developing brain. In agreement with this essential role, deficiency of Obp44a leads to anatomical and behavioral deficits in adult animals and elevated oxidized lipid levels. Collectively, our findings unveil the crucial involvement of a noncanonical lipid chaperone to shuttle fatty acids within and outside the brain, as needed to maintain a healthy brain lipid environment. These findings could inspire the design of novel approaches to restore lipid homeostasis that is dysregulated in CNS diseases.