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Fatty acid binding proteins are novel modulators of synaptic epoxyeicosatrienoic acid signaling in the brain

Fatty acid binding proteins (FABPs) govern intracellular lipid transport to cytosolic organelles and nuclear receptors. More recently, FABP5 has emerged as a key regulator of synaptic endocannabinoid signaling, suggesting that FABPs may broadly regulate the signaling of neuroactive lipids in the bra...

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Autores principales: Glaser, Sherrye T., Jayanetti, Kalani, Oubraim, Saida, Hillowe, Andrew, Frank, Elena, Jong, Jason, Wang, Liqun, Wang, Hehe, Ojima, Iwao, Haj-Dahmane, Samir, Kaczocha, Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10502087/
https://www.ncbi.nlm.nih.gov/pubmed/37709856
http://dx.doi.org/10.1038/s41598-023-42504-4
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author Glaser, Sherrye T.
Jayanetti, Kalani
Oubraim, Saida
Hillowe, Andrew
Frank, Elena
Jong, Jason
Wang, Liqun
Wang, Hehe
Ojima, Iwao
Haj-Dahmane, Samir
Kaczocha, Martin
author_facet Glaser, Sherrye T.
Jayanetti, Kalani
Oubraim, Saida
Hillowe, Andrew
Frank, Elena
Jong, Jason
Wang, Liqun
Wang, Hehe
Ojima, Iwao
Haj-Dahmane, Samir
Kaczocha, Martin
author_sort Glaser, Sherrye T.
collection PubMed
description Fatty acid binding proteins (FABPs) govern intracellular lipid transport to cytosolic organelles and nuclear receptors. More recently, FABP5 has emerged as a key regulator of synaptic endocannabinoid signaling, suggesting that FABPs may broadly regulate the signaling of neuroactive lipids in the brain. Herein, we demonstrate that brain-expressed FABPs (FABP3, FABP5, and FABP7) interact with epoxyeicosatrienoic acids (EETs) and the peroxisome proliferator-activated receptor gamma agonist 15-deoxy-Δ(12,14)-Prostaglandin J2 (15d-PGJ(2)). Among these lipids, EETs displayed highest affinities for FABP3 and FABP5, and 11,12-EET was identified as the preferred FABP ligand. Similarly, 15d-PGJ(2) interacted with FABP3 and FABP5 while binding to FABP7 was markedly lower. Molecular modeling revealed unique binding interactions of the ligands within the FABP binding pockets and highlighted major contributions of van der Waals clashes and acyl chain solvent exposure in dictating FABP affinity and specificity. Functional studies demonstrated that endogenous EETs gate the strength of CA1 hippocampal glutamate synapses and that this function was impaired following FABP inhibition. As such, the present study reveals that FABPs control EET-mediated synaptic gating, thereby expanding the functional roles of this protein family in regulating neuronal lipid signaling.
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spelling pubmed-105020872023-09-16 Fatty acid binding proteins are novel modulators of synaptic epoxyeicosatrienoic acid signaling in the brain Glaser, Sherrye T. Jayanetti, Kalani Oubraim, Saida Hillowe, Andrew Frank, Elena Jong, Jason Wang, Liqun Wang, Hehe Ojima, Iwao Haj-Dahmane, Samir Kaczocha, Martin Sci Rep Article Fatty acid binding proteins (FABPs) govern intracellular lipid transport to cytosolic organelles and nuclear receptors. More recently, FABP5 has emerged as a key regulator of synaptic endocannabinoid signaling, suggesting that FABPs may broadly regulate the signaling of neuroactive lipids in the brain. Herein, we demonstrate that brain-expressed FABPs (FABP3, FABP5, and FABP7) interact with epoxyeicosatrienoic acids (EETs) and the peroxisome proliferator-activated receptor gamma agonist 15-deoxy-Δ(12,14)-Prostaglandin J2 (15d-PGJ(2)). Among these lipids, EETs displayed highest affinities for FABP3 and FABP5, and 11,12-EET was identified as the preferred FABP ligand. Similarly, 15d-PGJ(2) interacted with FABP3 and FABP5 while binding to FABP7 was markedly lower. Molecular modeling revealed unique binding interactions of the ligands within the FABP binding pockets and highlighted major contributions of van der Waals clashes and acyl chain solvent exposure in dictating FABP affinity and specificity. Functional studies demonstrated that endogenous EETs gate the strength of CA1 hippocampal glutamate synapses and that this function was impaired following FABP inhibition. As such, the present study reveals that FABPs control EET-mediated synaptic gating, thereby expanding the functional roles of this protein family in regulating neuronal lipid signaling. Nature Publishing Group UK 2023-09-14 /pmc/articles/PMC10502087/ /pubmed/37709856 http://dx.doi.org/10.1038/s41598-023-42504-4 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Glaser, Sherrye T.
Jayanetti, Kalani
Oubraim, Saida
Hillowe, Andrew
Frank, Elena
Jong, Jason
Wang, Liqun
Wang, Hehe
Ojima, Iwao
Haj-Dahmane, Samir
Kaczocha, Martin
Fatty acid binding proteins are novel modulators of synaptic epoxyeicosatrienoic acid signaling in the brain
title Fatty acid binding proteins are novel modulators of synaptic epoxyeicosatrienoic acid signaling in the brain
title_full Fatty acid binding proteins are novel modulators of synaptic epoxyeicosatrienoic acid signaling in the brain
title_fullStr Fatty acid binding proteins are novel modulators of synaptic epoxyeicosatrienoic acid signaling in the brain
title_full_unstemmed Fatty acid binding proteins are novel modulators of synaptic epoxyeicosatrienoic acid signaling in the brain
title_short Fatty acid binding proteins are novel modulators of synaptic epoxyeicosatrienoic acid signaling in the brain
title_sort fatty acid binding proteins are novel modulators of synaptic epoxyeicosatrienoic acid signaling in the brain
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10502087/
https://www.ncbi.nlm.nih.gov/pubmed/37709856
http://dx.doi.org/10.1038/s41598-023-42504-4
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