ArticleThe Journal of biological chemistry2015
Proteasomal modulation of cellular SNAT2 (SLC38A2) abundance and function by unsaturated fatty acid availability.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 43 citations in OpenAlex.
- CHOP upregulation and dysregulation of the mature form of the SNAT2 amino acid transporter in the placentas from small for gestational age newborns.Cell communication and signaling : CCS · 2023Article
- Transcriptomic Responses to Polymyxin B and Analogues in Human Kidney Tubular Cells.Antibiotics (Basel, Switzerland) · 2023Article
- Sodium-Dependent Neutral Amino Acid Transporter 2 Can Serve as a Tertiary Carrier for l-Type Amino Acid Transporter 1-Utilizing Prodrugs.Molecular pharmaceutics · 2023Article
- SNAT2 is responsible for hyperosmotic induced sarcosine and glycine uptake in human prostate PC-3 cells.Pflugers Archiv : European journal of physiology · 2022Article
- Fetal sex modulates placental microRNA expression, potential microRNA-mRNA interactions, and levels of amino acid transporter expression and substrates: INFAT study subpopulation analysis of n-3 LCPUFA intervention during pregnancy and associations with offspring body composition.BMC molecular and cell biology · 2021Article
- Increased expression of glutamine transporter SNAT2/SLC38A2 promotes glutamine dependence and oxidative stress resistance, and is associated with worse prognosis in triple-negative breast cancer.British journal of cancer · 2021Article
- Dexamethasone acutely suppresses the anabolic SNAT2/SLC38A2 amino acid transporter protein in L6-G8C5 rat skeletal muscle cells.FASEB bioAdvances · 2021Article
- A selectively suppressing amino acid transporter: Sodium-coupled neutral amino acid transporter 2 inhibits cell growth and mammalian target of rapamycin complex 1 pathway in skeletal muscle cells.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2020Article
- Selective Alanine Transporter Utilization Creates a Targetable Metabolic Niche in Pancreatic Cancer.Cancer discovery · 2020Article
- Targeted Degradation of SLC Transporters Reveals Amenability of Multi-Pass Transmembrane Proteins to Ligand-Induced Proteolysis.Cell chemical biology · 2020Article
- Enhanced biodiversity of gut flora and feed efficiency in pond cultured tilapia under reduced frequency feeding strategies.PloS one · 2020Article
- TFEB controls retromer expression in response to nutrient availability.The Journal of cell biology · 2019Article
- Hypoxia-induced switch in SNAT2/SLC38A2 regulation generates endocrine resistance in breast cancer.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Glutamine Supplementation Ameliorates Chronic Stress-induced Reductions in Glutamate and Glutamine Transporters in the Mouse Prefrontal Cortex.Experimental neurobiology · 2019Article
- Effects of Sodium and Amino Acid Substrate Availability upon the Expression and Stability of the SNAT2 (SLC38A2) Amino Acid Transporter.Frontiers in pharmacology · 2018Article
- Multiple Transceptors for Macro- and Micro-Nutrients Control Diverse Cellular Properties Through the PKA Pathway in Yeast: A Paradigm for the Rapidly Expanding World of Eukaryotic Nutrient Transceptors Up to Those in Human Cells.Frontiers in pharmacology · 2018Review
- Lipid modulation of skeletal muscle mass and function.Journal of cachexia, sarcopenia and muscle · 2017Review
- Regulation of amino acid transporter trafficking by mTORC1 in primary human trophoblast cells is mediated by the ubiquitin ligase Nedd4-2.Clinical science (London, England : 1979) · 2016Article
- Characterization of 5-(2-F1000Research · 2016Article
- TNF-α stimulates System A amino acid transport in primary human trophoblast cells mediated by p38 MAPK signaling.Physiological reports · 2015Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Expression and activity of the System A/SNAT2 (SLC38A2) amino acid transporter is up-regulated by amino acid starvation and hypertonicity by a mechanism dependent on both ATF4-mediated transcription of the SLC38A2 gene and enhanced stabilization of SNAT2 itself, which forms part of an integrated cellular stress response to nutrient deprivation and osmotic stress. Here we demonstrate that this adaptive increase in System A function is restrained in cells subjected to prior incubation with linoleic acid (LOA, an unsaturated C18:2 fatty acid) for 24 h. While fatty acid treatment had no detectable effect upon stress-induced SNAT2 or ATF4 gene transcription, the associated increase in SNAT2 protein/membrane transport activity were strongly suppressed in L6 myotubes or HeLa cells preincubated with LOA. Cellular ubiquitination of many proteins was increased by LOA and although the fatty acid-induced loss of SNAT2 could be attenuated by proteasomal inhibition, the functional increase in System A transport activity associated with amino acid starvation/hypertonicity that depends upon processing/maturation and delivery of SNAT2 to the cell surface could not be rescued. LOA up-regulated cellular expression of Nedd4.2, an E3-ligase implicated in SNAT2 ubiquitination, but shRNA-directed Nedd4.2 gene silencing could not curb fatty acid-induced loss of SNAT2 adaptation. However, expression of SNAT2 in which seven putative lysyl-ubiquitination sites in the cytoplasmic N-terminal domain were mutated to alanine protected SNAT2 against LOA-induced proteasomal degradation. Collectively, our findings indicate that increased availability of unsaturated fatty acids can compromise the stress-induced induction/adaptation in SNAT2 expression and function by promoting its degradation via the ubiquitin-proteasome system.
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