Effects of Sodium and Amino Acid Substrate Availability upon the Expression and Stability of the SNAT2 (SLC38A2) Amino Acid Transporter

Frontiers in Pharmacology
Thorsten M HoffmannHarinder S Hundal

Abstract

The SNAT2 (SLC38A2) System A amino acid transporter mediates Na+-coupled cellular uptake of small neutral α-amino acids (AAs) and is extensively regulated in response to humoral and nutritional cues. Understanding the basis of such regulation is important given that AA uptakeviaSNAT2 has been linked to activation of mTORC1; a major controller of many important cellular processes including, for example, mRNA translation, lipid synthesis, and autophagy and whose dysregulation has been implicated in the development of cancer and conditions such as obesity and type 2 diabetes. Extracellular AA withdrawal induces an adaptive upregulation of SNAT2 gene transcription and SNAT2 protein stability but, as yet, the sensing mechanism(s) that initiate this response remain poorly understood although interactions between SNAT2 and its substrates may play a vital role. Herein, we have explored how changes in substrate (AA and Na+) availability impact upon the adaptive regulation of SNAT2 in HeLa cells. We show that while AA deprivation induces SNAT2 gene expression, this induction was not apparent if extracellular Na+was removed during the AA withdrawal period. Furthermore, we show that the increase in SNAT2 protein stability associated with A...Continue Reading

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Citations

Nov 7, 2019·The Journal of Cell Biology·Rachel CurnockPeter J Cullen
May 30, 2019·The Journal of Experimental Biology·Stephanie N CatyLauren A O'Connell
Jul 13, 2020·Cellular and Molecular Neurobiology·Wenchen RuanJingwei Li
Mar 14, 2020·International Journal of Molecular Sciences·Martina ChiuOvidio Bussolati
Mar 15, 2020·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Anna Alvarez-GuaitaCarles Rentero
Nov 24, 2020·American Journal of Physiology. Endocrinology and Metabolism·Laura Velázquez-VillegasVictor M Ortiz-Ortega
May 1, 2021·Frontiers in Molecular Biosciences·Stephen J FairweatherStefan Bröer

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Methods Mentioned

BETA
Transfection
PCR
Assay
X-Ray
Ubiquitination

Software Mentioned

ImageJ
GraphPad Prism

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