SLC38A10 Regulate Glutamate Homeostasis and Modulate the AKT/TSC2/mTOR Pathway in Mouse Primary Cortex Cells
Glutamate acts as a critical regulator of neurotransmitter balance, recycling, synaptic function and homeostasis in the brain and glutamate transporters control glutamate levels in the brain. SLC38A10 is a member of the SLC38 family and regulates protein synthesis and cellular stress responses. Here...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2022.854397/full |
| _version_ | 1818348590100119552 |
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| author | Rekha Tripathi Tanya Aggarwal Frida A. Lindberg Anna H. Klemm Robert Fredriksson |
| author_facet | Rekha Tripathi Tanya Aggarwal Frida A. Lindberg Anna H. Klemm Robert Fredriksson |
| author_sort | Rekha Tripathi |
| collection | DOAJ |
| description | Glutamate acts as a critical regulator of neurotransmitter balance, recycling, synaptic function and homeostasis in the brain and glutamate transporters control glutamate levels in the brain. SLC38A10 is a member of the SLC38 family and regulates protein synthesis and cellular stress responses. Here, we uncover the role of SLC38A10 as a transceptor involved in glutamate-sensing signaling pathways that control both the glutamate homeostasis and mTOR-signaling. The culture of primary cortex cells from SLC38A10 knockout mice had increased intracellular glutamate. In addition, under nutrient starvation, KO cells had an impaired response in amino acid-dependent mTORC1 signaling. Combined studies from transcriptomics, protein arrays and metabolomics established that SLC38A10 is involved in mTOR signaling and that SLC38A10 deficient primary cortex cells have increased protein synthesis. Metabolomic data showed decreased cholesterol levels, changed fatty acid synthesis, and altered levels of fumaric acid, citrate, 2-oxoglutarate and succinate in the TCA cycle. These data suggests that SLC38A10 may act as a modulator of glutamate homeostasis, and mTOR-sensing and loss of this transceptor result in lower cholesterol, which could have implications in neurodegenerative diseases. |
| first_indexed | 2024-12-13T17:52:28Z |
| format | Article |
| id | doaj.art-ac78f42067e2414da2002a0ef517dbc3 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-13T17:52:28Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-ac78f42067e2414da2002a0ef517dbc32022-12-21T23:36:28ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-04-011010.3389/fcell.2022.854397854397SLC38A10 Regulate Glutamate Homeostasis and Modulate the AKT/TSC2/mTOR Pathway in Mouse Primary Cortex CellsRekha Tripathi0Tanya Aggarwal1Frida A. Lindberg2Anna H. Klemm3Robert Fredriksson4Department of Pharmaceutical Bioscience, Unit of Molecular Neuropharmacology, Uppsala University, Uppsala, SwedenDepartment of Pharmaceutical Bioscience, Unit of Molecular Neuropharmacology, Uppsala University, Uppsala, SwedenDepartment of Pharmaceutical Bioscience, Unit of Molecular Neuropharmacology, Uppsala University, Uppsala, SwedenBioImage Informatics Facility, SciLifeLab, Division of Visual Information and Interaction, Department of Information Technology, Uppsala, SwedenDepartment of Pharmaceutical Bioscience, Unit of Molecular Neuropharmacology, Uppsala University, Uppsala, SwedenGlutamate acts as a critical regulator of neurotransmitter balance, recycling, synaptic function and homeostasis in the brain and glutamate transporters control glutamate levels in the brain. SLC38A10 is a member of the SLC38 family and regulates protein synthesis and cellular stress responses. Here, we uncover the role of SLC38A10 as a transceptor involved in glutamate-sensing signaling pathways that control both the glutamate homeostasis and mTOR-signaling. The culture of primary cortex cells from SLC38A10 knockout mice had increased intracellular glutamate. In addition, under nutrient starvation, KO cells had an impaired response in amino acid-dependent mTORC1 signaling. Combined studies from transcriptomics, protein arrays and metabolomics established that SLC38A10 is involved in mTOR signaling and that SLC38A10 deficient primary cortex cells have increased protein synthesis. Metabolomic data showed decreased cholesterol levels, changed fatty acid synthesis, and altered levels of fumaric acid, citrate, 2-oxoglutarate and succinate in the TCA cycle. These data suggests that SLC38A10 may act as a modulator of glutamate homeostasis, and mTOR-sensing and loss of this transceptor result in lower cholesterol, which could have implications in neurodegenerative diseases.https://www.frontiersin.org/articles/10.3389/fcell.2022.854397/fullsolute carriers transporterprimary cortex culturesstarvationSLC38A10mTOR |
| spellingShingle | Rekha Tripathi Tanya Aggarwal Frida A. Lindberg Anna H. Klemm Robert Fredriksson SLC38A10 Regulate Glutamate Homeostasis and Modulate the AKT/TSC2/mTOR Pathway in Mouse Primary Cortex Cells Frontiers in Cell and Developmental Biology solute carriers transporter primary cortex cultures starvation SLC38A10 mTOR |
| title | SLC38A10 Regulate Glutamate Homeostasis and Modulate the AKT/TSC2/mTOR Pathway in Mouse Primary Cortex Cells |
| title_full | SLC38A10 Regulate Glutamate Homeostasis and Modulate the AKT/TSC2/mTOR Pathway in Mouse Primary Cortex Cells |
| title_fullStr | SLC38A10 Regulate Glutamate Homeostasis and Modulate the AKT/TSC2/mTOR Pathway in Mouse Primary Cortex Cells |
| title_full_unstemmed | SLC38A10 Regulate Glutamate Homeostasis and Modulate the AKT/TSC2/mTOR Pathway in Mouse Primary Cortex Cells |
| title_short | SLC38A10 Regulate Glutamate Homeostasis and Modulate the AKT/TSC2/mTOR Pathway in Mouse Primary Cortex Cells |
| title_sort | slc38a10 regulate glutamate homeostasis and modulate the akt tsc2 mtor pathway in mouse primary cortex cells |
| topic | solute carriers transporter primary cortex cultures starvation SLC38A10 mTOR |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2022.854397/full |
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