Cargando…
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...
Autores principales: | , , , , , , , , , , |
---|---|
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 |
_version_ | 1785106243973545984 |
---|---|
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. |
format | Online Article Text |
id | pubmed-10502087 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT glasersherryet fattyacidbindingproteinsarenovelmodulatorsofsynapticepoxyeicosatrienoicacidsignalinginthebrain AT jayanettikalani fattyacidbindingproteinsarenovelmodulatorsofsynapticepoxyeicosatrienoicacidsignalinginthebrain AT oubraimsaida fattyacidbindingproteinsarenovelmodulatorsofsynapticepoxyeicosatrienoicacidsignalinginthebrain AT hilloweandrew fattyacidbindingproteinsarenovelmodulatorsofsynapticepoxyeicosatrienoicacidsignalinginthebrain AT frankelena fattyacidbindingproteinsarenovelmodulatorsofsynapticepoxyeicosatrienoicacidsignalinginthebrain AT jongjason fattyacidbindingproteinsarenovelmodulatorsofsynapticepoxyeicosatrienoicacidsignalinginthebrain AT wangliqun fattyacidbindingproteinsarenovelmodulatorsofsynapticepoxyeicosatrienoicacidsignalinginthebrain AT wanghehe fattyacidbindingproteinsarenovelmodulatorsofsynapticepoxyeicosatrienoicacidsignalinginthebrain AT ojimaiwao fattyacidbindingproteinsarenovelmodulatorsofsynapticepoxyeicosatrienoicacidsignalinginthebrain AT hajdahmanesamir fattyacidbindingproteinsarenovelmodulatorsofsynapticepoxyeicosatrienoicacidsignalinginthebrain AT kaczochamartin fattyacidbindingproteinsarenovelmodulatorsofsynapticepoxyeicosatrienoicacidsignalinginthebrain |