scholarly journals Functional Dynamics of Glutamate/Amino Acid Transporters of the Solute Carrier 1 Family

2015 ◽  
Vol 108 (2) ◽  
pp. 199a
Author(s):  
Christof Grewer
Keyword(s):  
Amino Acid ◽  
Amino Acid Transporters ◽  
Functional Dynamics ◽  
Solute Carrier

scholarly journals Expression of solute carrier 7A4 (SLC7A4) in the plasma membrane is not sufficient to mediate amino acid transport activity

2002 ◽  
Vol 364 (3) ◽  
pp. 767-775 ◽  
Author(s):  
Sabine WOLF ◽  
Annette JANZEN ◽  
Nicole VÉKONY ◽  
Ursula MARTINÉ ◽  
Dennis STRAND ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Amino Acid ◽  
Protein Expression ◽  
Amino Acid Transport ◽  
Fluorescent Protein ◽  
Xenopus Laevis Oocytes ◽  
Amino Acid Transporters ◽  
Acid Transport ◽  
Transport Activity ◽  
Solute Carrier

Member 4 of human solute carrier family 7 (SLC7A4) exhibits significant sequence homology with the SLC7 subfamily of human cationic amino acid transporters (hCATs) [Sperandeo, Borsani, Incerti, Zollo, Rossi, Zuffardi, Castaldo, Taglialatela, Andria and Sebastio (1998) Genomics 49, 230–236]. It is therefore often referred to as hCAT-4 even though no convincing transport activity has been shown for this protein. We expressed SLC7A4 in Xenopus laevis oocytes, but could not detect any transport activity for cationic, neutral or anionic amino acids or for the polyamine putrescine. In addition, human glioblastoma cells stably overexpressing a fusion protein between SLC7A4 and the enhanced green fluorescent protein (EGFP) did not exhibit an increased transport activity for l-arginine. The lack of transport activity was not due to a lack of SLC7A4 protein expression in the plasma membrane, as in both cell types SLC7A4-EGFP exhibited a similar subcellular localization and level of protein expression as functional hCAT-EGFP proteins. The expression of SLC7A4 can be induced in NT2 teratocarcinoma cells by treatment with retinoic acid. However, also for this endogenously expressed SLC7A4, we could not detect any transport activity for l-arginine. Our data demonstrate that the expression of SLC7A4 in the plasma membrane is not sufficient to induce an amino acid transport activity in X. laevis oocytes or human cells. Therefore, SLC7A4 is either not an amino acid transporter or it needs additional (protein) factor(s) to be functional.

scholarly journals Lysosomal amino acid transporters as key players in inflammatory diseases

2021 ◽  
Author(s):  
Noriko Toyama-Sorimachi ◽  
Toshihiko Kobayashi
Keyword(s):  
Signal Transduction ◽  
Amino Acid ◽  
Immune Cells ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Metabolic Adaptation ◽  
Amino Acid Transporters ◽  
Proof Of Concept ◽  
Immune Mediated ◽  
Solute Carrier

Abstract Controlling inflammation can alleviate immune-mediated, lifestyle-related and neurodegenerative diseases. The endolysosome system plays critical roles in inflammatory responses. Endolysosomes function as signal transduction hubs to convert various environmental danger signals into gene expression, enabling metabolic adaptation of immune cells and efficient orchestration of inflammation. Solute carrier family 15 member 3 (SLC15A3) and member 4 (SLC15A4) are endolysosome-resident amino acid transporters that are preferentially expressed in immune cells. These transporters play essential roles in signal transduction through endolysosomes, and the loss of either transporter can alleviate multiple inflammatory diseases because of perturbed endolysosome-dependent signaling events, including inflammatory and metabolic signaling. Here, we summarize the findings leading to a proof-of-concept for anti-inflammatory strategies based on targeting SLC15 transporters.

The Evolutionary History and Tissue Mapping of Amino Acid Transporters Belonging to Solute Carrier Families SLC32, SLC36, and SLC38

2008 ◽  
Vol 35 (2) ◽  
pp. 179-193 ◽  
Author(s):  
Björn E. Sundberg ◽  
Elin Wååg ◽  
Josefin A. Jacobsson ◽  
Olga Stephansson ◽  
Juris Rumaks ◽  
...  
Keyword(s):  
Amino Acid ◽  
Evolutionary History ◽  
Amino Acid Transporters ◽  
Solute Carrier ◽  
Tissue Mapping

scholarly journals Amino Acid Transporters on the Guard of Cell Genome and Epigenome

Cancers ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 125
Author(s):  
Uğur Kahya ◽  
Ayşe Sedef Köseer ◽  
Anna Dubrovska
Keyword(s):  
Amino Acid ◽  
Cancer Metabolism ◽  
Tumor Imaging ◽  
Redox Homeostasis ◽  
Amino Acid Uptake ◽  
Metabolic Reprogramming ◽  
Tumor Evolution ◽  
Amino Acid Transporters ◽  
Acid Uptake ◽  
Growth And Survival

Tumorigenesis is driven by metabolic reprogramming. Oncogenic mutations and epigenetic alterations that cause metabolic rewiring may also upregulate the reactive oxygen species (ROS). Precise regulation of the intracellular ROS levels is critical for tumor cell growth and survival. High ROS production leads to the damage of vital macromolecules, such as DNA, proteins, and lipids, causing genomic instability and further tumor evolution. One of the hallmarks of cancer metabolism is deregulated amino acid uptake. In fast-growing tumors, amino acids are not only the source of energy and building intermediates but also critical regulators of redox homeostasis. Amino acid uptake regulates the intracellular glutathione (GSH) levels, endoplasmic reticulum stress, unfolded protein response signaling, mTOR-mediated antioxidant defense, and epigenetic adaptations of tumor cells to oxidative stress. This review summarizes the role of amino acid transporters as the defender of tumor antioxidant system and genome integrity and discusses them as promising therapeutic targets and tumor imaging tools.

scholarly journals Pichia pastoris and the Recombinant Human Heterodimeric Amino Acid Transporter 4F2hc-LAT1: From Clone Selection to Pure Protein

2021 ◽  
Vol 4 (3) ◽  
pp. 51
Author(s):  
Satish Kantipudi ◽  
Daniel Harder ◽  
Sara Bonetti ◽  
Dimitrios Fotiadis ◽  
Jean-Marc Jeckelmann
Keyword(s):  
Amino Acid ◽  
Pichia Pastoris ◽  
Protein Complexes ◽  
Amino Acid Transporter ◽  
Amino Acid Transporters ◽  
Expression Host ◽  
Amino Acids And Derivatives ◽  
Heterodimeric Complex ◽  
Acid Transporter ◽  
And Function

Heterodimeric amino acid transporters (HATs) are protein complexes composed of two subunits, a heavy and a light subunit belonging to the solute carrier (SLC) families SLC3 and SLC7. HATs transport amino acids and derivatives thereof across the plasma membrane. The human HAT 4F2hc-LAT1 is composed of the type-II membrane N-glycoprotein 4F2hc (SLC3A2) and the L-type amino acid transporter LAT1 (SLC7A5). 4F2hc-LAT1 is medically relevant, and its dysfunction and overexpression are associated with autism and tumor progression. Here, we provide a general applicable protocol on how to screen for the best membrane transport protein-expressing clone in terms of protein amount and function using Pichia pastoris as expression host. Furthermore, we describe an overexpression and purification procedure for the production of the HAT 4F2hc-LAT1. The isolated heterodimeric complex is pure, correctly assembled, stable, binds the substrate L-leucine, and is thus properly folded. Therefore, this Pichia pastoris-derived recombinant human 4F2hc-LAT1 sample can be used for downstream biochemical and biophysical characterizations.

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