Search results for "Amino acid transporter"
showing 10 items of 45 documents
Direct Sensing of Nutrients via a LAT1-like Transporter in Drosophila Insulin-Producing Cells
2016
Summary Dietary leucine has been suspected to play an important role in insulin release, a hormone that controls satiety and metabolism. The mechanism by which insulin-producing cells (IPCs) sense leucine and regulate insulin secretion is still poorly understood. In Drosophila, insulin-like peptides (DILP2 and DILP5) are produced by brain IPCs and are released in the hemolymph after leucine ingestion. Using Ca2+-imaging and ex vivo cultured larval brains, we demonstrate that IPCs can directly sense extracellular leucine levels via minidiscs (MND), a leucine transporter. MND knockdown in IPCs abolished leucine-dependent changes, including loss of DILP2 and DILP5 in IPC bodies, consistent wit…
Cationic Amino Acid Transporter-1-Mediated Arginine Uptake Is Essential for Chronic Lymphocytic Leukemia Cell Proliferation and Viability
2019
Interfering with tumor metabolism by specifically restricting the availability of extracellular nutrients is a rapidly emerging field of cancer research. A variety of tumor entities depend on the uptake of the amino acid arginine since they have lost the ability to synthesize it endogenously, that is they do not express the rate limiting enzyme for arginine synthesis, argininosuccinate synthase (ASS). Arginine transport through the plasma membrane of mammalian cells is mediated by eight different transporters that belong to two solute carrier (SLC) families. In the present study we found that the proliferation of primary as well as immortalized chronic lymphocytic leukemia (CLL) cells depen…
Induced arginine transport via cationic amino acid transporter-1 is necessary for human T-cell proliferation
2015
Availability of the semiessential amino acid arginine is fundamental for the efficient function of human T lymphocytes. Tumor-associated arginine deprivation, mainly induced by myeloid-derived suppressor cells, is a central mechanism of tumor immune escape from T-cell-mediated antitumor immune responses. We thus assumed that transmembranous transport of arginine must be crucial for T-cell function and studied which transporters are responsible for arginine influx into primary human T lymphocytes. Here, we show that activation via CD3 and CD28 induces arginine transport into primary human T cells. Both naive and memory CD4(+) T cells as well as CD8(+) T cells specifically upregulated the hum…
The Amino Acid Transporter JhI-21 Coevolves with Glutamate Receptors, Impacts NMJ Physiology, and Influences Locomotor Activity in Drosophila Larvae
2015
AbstractChanges in synaptic physiology underlie neuronal network plasticity and behavioral phenomena, which are adjusted during development. The Drosophila larval glutamatergic neuromuscular junction (NMJ) represents a powerful synaptic model to investigate factors impacting these processes. Amino acids such as glutamate have been shown to regulate Drosophila NMJ physiology by modulating the clustering of postsynaptic glutamate receptors and thereby regulating the strength of signal transmission from the motor neuron to the muscle cell. To identify amino acid transporters impacting glutmatergic signal transmission, we used Evolutionary Rate Covariation (ERC), a recently developed bioinforma…
Reconstitution of T Cell Proliferation under Arginine Limitation: Activated Human T Cells Take Up Citrulline via L-Type Amino Acid Transporter 1 and …
2017
In the tumor microenvironment, arginine is metabolized by arginase-expressing myeloid cells. This arginine depletion profoundly inhibits T cell functions and is crucially involved in tumor-induced immunosuppression. Reconstitution of adaptive immune functions in the context of arginase-mediated tumor immune escape is a promising therapeutic strategy to boost the immunological anti-tumor response. Arginine can be recycled in certain mammalian tissues from citrulline via argininosuccinate in a two-step enzymatic process involving the enzymes argininosuccinate synthase (ASS) and argininosuccinate lyase (ASL). Here we demonstrate that anti-CD3/anti-CD28-activated human primary CD4+ and CD8+ T c…
Glut-1 Expression and In Situ CD1a/CD57 Immunologic Deficit in Keratoacanthoma and Squamous Cell Carcinoma of Immunocompetent Patients
2011
It is not easy to reach a differential diagnosis between keratoacanthoma (KA) and squamous cell carcinoma (SCC) and furthermore there is still considerable discussion about the relationship of these 2 tumors with immunity. To facilitate such a diagnosis, we assessed the Glut-1 antibody, reported to be strongly and diffusely expressed in SCC but never assessed in KA. We studied 43 lesions of immunocompetent patients: 17 SCCs, 13 typical KAs (tKAs), and 13 atypical KAs (aKAs), with histologic features of SCC in less than 30% of the lesions. In tKA, Glut-1 stained only the basal layers of the squamous nests (basal pattern) whereas in SCC the squamous nests were randomly and diffusely stained (…
Activation of classical protein kinase C decreases transport via systems y+and y+L
2007
Activation of protein kinase C (PKC) downregulates the human cationic amino acid transporters hCAT-1 (SLC7A1) and hCAT-3 (SLC7A3) (Rotmann A, Strand D, Martiné U, Closs EI. J Biol Chem 279: 54185–54192, 2004; Rotmann A, Vekony N, Gassner D, Niegisch G, Strand D, Martine U, Closs EI. Biochem J 395: 117–123, 2006). However, others found that PKC increased arginine transport in various mammalian cell types, suggesting that the expression of different arginine transporters might be responsible for the opposite PKC effects. We thus investigated the consequence of PKC activation by phorbol-12-myristate-13-acetate (PMA) in various human cell lines expressing leucine-insensitive system y+[hCAT-1, h…
Protein Kinase C Activation Promotes the Internalization of the Human Cationic Amino Acid Transporter hCAT-1
2004
The human cationic amino acid transporter hCAT-1 is almost ubiquitously expressed and probably the most important entity for supplying cells with extracellular arginine, lysine, and ornithine. We have previously shown that hCAT-1-mediated transport is decreased after protein kinase C (PKC) activation by phorbol 12-myristate 13-acetate (PMA) (Graf, P., Forstermann, U., and Closs, E. I. (2001) Br. J. Pharmacol. 132, 1193-1200). In the present study, we examined the mechanism of this down-regulation. In both Xenopus laevis oocytes and U373MG glioblastoma cells, PMA treatment promoted the internalization of hCAT-1 (fused to the enhanced green fluorescence protein (EGFP)) as visualized by fluore…
Voltage dependence of L-arginine transport by hCAT-2A and hCAT-2B expressed in oocytes from Xenopus laevis.
2000
Membrane potential and currents were investigated with the two-electrode voltage-clamp technique in Xenopus laevisoocytes expressing hCAT-2A or hCAT-2B, the splice variants of the human cationic amino acid transporter hCAT-2. Both hCAT-2A- and hCAT-2B-expressing oocytes exhibited a negative extracellularl-arginine concentration ([l-Arg]o)-sensitive membrane potential, additive to the K+diffusion potential, when cells were incubated in Leibovitz medium (containing 1.45 mM l-Arg and 0.25 mM l-lysine). The two carrier proteins produced inward and outward currents, which were dependent on the l-Arg gradient and membrane potential. Ion substitution experiments showed that the hCAT-induced curren…
Polyamines Impair Immunity to Helicobacter pylori by Inhibiting L-Arginine Uptake Required for Nitric Oxide Production
2010
International audience; BACKGROUND & AIMS: Helicobacter pylori-induced immune responses fail to eradicate the bacterium. Nitric oxide (NO) can kill H pylori. However, translation of inducible NO synthase (iNOS) and NO generation by H pylori-stimulated macrophages is inhibited by the polyamine spermine derived from ornithine decarboxylase (ODC), and is dependent on availability of the iNOS substrate L-arginine (L-Arg). We determined if spermine inhibits iNOS-mediated immunity by reducing L-Arg uptake into macrophages. METHODS: Levels of the inducible cationic amino acid transporter (CAT) 2, ODC, and iNOS were measured in macrophages and H pylori gastritis tissues. L-Arg uptake, iNOS expressi…