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Glia-derived secretory fatty acid binding protein Obp44a regulates lipid storage and efflux in the developing Drosophila brain.
Yin, Jun; Chen, Hsueh-Ling; Grigsby-Brown, Anna; He, Yi; Cotten, Myriam L; Short, Jacob; Dermady, Aidan; Lei, Jingce; Gibbs, Mary; Cheng, Ethan S; Zhang, Dean; Long, Caixia; Xu, Lele; Zhong, Tiffany; Abzalimov, Rinat; Haider, Mariam; Sun, Rong; He, Ye; Zhou, Qiangjun; Tjandra, Nico; Yuan, Quan.
Afiliação
  • Yin J; Dendrite Morphogenesis and Plasticity Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.
  • Chen HL; Dendrite Morphogenesis and Plasticity Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.
  • Grigsby-Brown A; Dendrite Morphogenesis and Plasticity Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.
  • He Y; Fermentation Facility, Biochemistry and Biophysics Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
  • Cotten ML; Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR.
  • Short J; Dendrite Morphogenesis and Plasticity Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.
  • Dermady A; Dendrite Morphogenesis and Plasticity Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.
  • Lei J; Dendrite Morphogenesis and Plasticity Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.
  • Gibbs M; Dendrite Morphogenesis and Plasticity Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.
  • Cheng ES; Dendrite Morphogenesis and Plasticity Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.
  • Zhang D; Dendrite Morphogenesis and Plasticity Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.
  • Long C; Dendrite Morphogenesis and Plasticity Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.
  • Xu L; Advanced Science Research Center, The City University of New York, New York, NY.
  • Zhong T; Ph.D. Program in Biology, The Graduate Center of the City University of New York, New York, NY.
  • Abzalimov R; Neuroscience Program, Princeton University, Princeton, NJ.
  • Haider M; Advanced Science Research Center, The City University of New York, New York, NY.
  • Sun R; Department of Cell and Developmental Biology, Vanderbilt Brain Institute, Center for Structural Biology, Vanderbilt Kennedy Center, Vanderbilt University, Nashville, TN.
  • He Y; Department of Cell and Developmental Biology, Vanderbilt Brain Institute, Center for Structural Biology, Vanderbilt Kennedy Center, Vanderbilt University, Nashville, TN.
  • Zhou Q; Advanced Science Research Center, The City University of New York, New York, NY.
  • Tjandra N; Ph.D. Program in Biology, The Graduate Center of the City University of New York, New York, NY.
  • Yuan Q; Department of Cell and Developmental Biology, Vanderbilt Brain Institute, Center for Structural Biology, Vanderbilt Kennedy Center, Vanderbilt University, Nashville, TN.
bioRxiv ; 2024 Apr 11.
Article em En | MEDLINE | ID: mdl-38645138
ABSTRACT
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.

Texto completo: 1 Bases de dados: MEDLINE Idioma: En Revista: BioRxiv Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Moldávia

Texto completo: 1 Bases de dados: MEDLINE Idioma: En Revista: BioRxiv Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Moldávia