AQR1 Gene (ORF YNL065w) Encodes a Plasma Membrane Transporter of the Major Facilitator Superfamily That Confers Resistance to Short-Chain Monocarboxylic Acids and Quinidine in Saccharomyces cerevisiae

2002 ◽  
Vol 292 (3) ◽  
pp. 741-748 ◽  
Author(s):  
Sandra Tenreiro ◽  
Patrı́cia A Nunes ◽  
Cristina A Viegas ◽  
Mónica S Neves ◽  
Miguel C Teixeira ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Plasma Membrane ◽  
Major Facilitator Superfamily ◽  
Short Chain ◽  
Membrane Transporter ◽  
Monocarboxylic Acids ◽  
Major Facilitator ◽  
Plasma Membrane Transporter

scholarly journals Resistance and Adaptation to Quinidine in Saccharomyces cerevisiae: Role of QDR1 (YIL120w), Encoding a Plasma Membrane Transporter of the Major Facilitator Superfamily Required for Multidrug Resistance

2001 ◽  
Vol 45 (5) ◽  
pp. 1528-1534 ◽  
Author(s):  
Patrı́cia A. Nunes ◽  
Sandra Tenreiro ◽  
Isabel Sá-Correia
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Plasma Membrane ◽  
Multidrug Resistance ◽  
Fluorescent Protein ◽  
Resistance Mechanisms ◽  
Major Facilitator Superfamily ◽  
Yeast Cells ◽  
Detectable Effect ◽  
Protein Fusion ◽  
Major Facilitator

ABSTRACT As predicted based on structural considerations, we show results indicating that the member of the major facilitator superfamily encoded by Saccharomyces cerevisiae open reading frameYIL120w is a multidrug resistance determinant. Yil120wp was implicated in yeast resistance to ketoconazole and quinidine, but not to the stereoisomer quinine; the gene was thus named QDR1. Qdr1p was proved to alleviate the deleterious effects of quinidine, revealed by the loss of cell viability following sudden exposure of the unadapted yeast population to the drug, and to allow the earlier eventual resumption of exponential growth under quinidine stress. However, QDR1 gene expression had no detectable effect on the susceptibility of yeast cells previously adapted to quinidine. Fluorescence microscopy observation of the distribution of the Qdr1-green fluorescent protein fusion protein in living yeast cells indicated that Qdr1p is a plasma membrane protein. We also show experimental evidence indicating that yeast adaptation to growth with quinidine involves the induction of active expulsion of the drug from preloaded cells, despite the fact that this antiarrhythmic and antimalarial quinoline ring-containing drug is not present in the yeast natural environment. However, we were not able to prove that Qdr1p is directly implicated in this export. Results clearly suggest that there are other unidentified quinidine resistance mechanisms that can be used in the absence of QDR1.

scholarly journals Untargeted Metabolomics Uncovers the Essential Lysine Transporter in Toxoplasma gondii

Metabolites ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 476
Author(s):  
Joachim Kloehn ◽  
Matteo Lunghi ◽  
Emmanuel Varesio ◽  
David Dubois ◽  
Dominique Soldati-Favre
Keyword(s):  
Amino Acids ◽  
Toxoplasma Gondii ◽  
Rna Degradation ◽  
Major Facilitator Superfamily ◽  
Untargeted Metabolomics ◽  
Apicomplexan Parasites ◽  
Obligate Intracellular ◽  
Intracellular Parasites ◽  
Major Facilitator ◽  
Plasma Membrane Transporter

Apicomplexan parasites are responsible for devastating diseases, including malaria, toxoplasmosis, and cryptosporidiosis. Current treatments are limited by emerging resistance to, as well as the high cost and toxicity of existing drugs. As obligate intracellular parasites, apicomplexans rely on the uptake of many essential metabolites from their host. Toxoplasma gondii, the causative agent of toxoplasmosis, is auxotrophic for several metabolites, including sugars (e.g., myo-inositol), amino acids (e.g., tyrosine), lipidic compounds and lipid precursors (cholesterol, choline), vitamins, cofactors (thiamine) and others. To date, only few apicomplexan metabolite transporters have been characterized and assigned a substrate. Here, we set out to investigate whether untargeted metabolomics can be used to identify the substrate of an uncharacterized transporter. Based on existing genome- and proteome-wide datasets, we have identified an essential plasma membrane transporter of the major facilitator superfamily in T. gondii—previously termed TgApiAT6-1. Using an inducible system based on RNA degradation, TgApiAT6-1 was depleted, and the mutant parasite’s metabolome was compared to that of non-depleted parasites. The most significantly reduced metabolite in parasites depleted in TgApiAT6-1 was identified as the amino acid lysine, for which T. gondii is predicted to be auxotrophic. Using stable isotope-labeled amino acids, we confirmed that TgApiAT6-1 is required for efficient lysine uptake. Our findings highlight untargeted metabolomics as a powerful tool to identify the substrate of orphan transporters.

scholarly journals The plasma membrane transporter SLC5A8 suppresses tumour progression through depletion of survivin without involving its transport function

2013 ◽  
Vol 450 (1) ◽  
pp. 169-178 ◽  
Author(s):  
Veena Coothankandaswamy ◽  
Selvakumar Elangovan ◽  
Nagendra Singh ◽  
Puttur D. Prasad ◽  
Muthusamy Thangaraju ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Cancer Cells ◽  
Histone Deacetylase Inhibitors ◽  
Tumour Progression ◽  
Ectopic Expression ◽  
Membrane Transporter ◽  
Transport Function ◽  
Plasma Membrane Transporter

SLC5A8 (solute carrier gene family 5A, member 8) is a sodium-coupled transporter for monocarboxylates. Among its substrates are the HDAC (histone deacetylase) inhibitors butyrate, propionate and pyruvate. Expression of SLC5A8 is silenced in cancers via DNA methylation, and ectopic expression of SLC5A8 in cancer cells induces apoptosis in the presence of its substrates that are HDAC inhibitors. In the present study we show that ectopic expression of SLC5A8 in cancer cells translocates the anti-apoptotic protein survivin to the plasma membrane through protein–protein interaction resulting in depletion of nuclear survivin and also decreases cellular levels of survivin through inhibition of transcription. These SLC5A8-induced changes in the location and levels of survivin result in cell-cycle arrest, disruption of the chromosome passenger complex involved in mitosis, induction of apoptosis and enhancement in chemosensitivity. These effects are seen independently of the transport function of SLC5A8 and histone acetylation status of the cell; in the presence of pyruvate, a SLC5A8 substrate and also an HDAC inhibitor, these effects are amplified. Ectopic expression of SLC5A8 in the breast cancer cell line MB231 inhibits the ability of cells to form colonies in vitro and to form tumours in mouse xenografts in vivo. The suppression of survivin transcription occurs independently of HDAC inhibition, and the underlying mechanism is associated with decreased phosphorylation of STAT3 (signal transducer and activator of transcription 3). The observed effects are specific for survivin with no apparent changes in expression of other inhibitor-of-apoptosis proteins. The present study unravels a novel, hitherto unrecognized, mechanism for the tumour-suppressive role of a plasma membrane transporter independent of its transport function.

scholarly journals Identification of anN-Acetylglucosamine Transporter That Mediates Hyphal Induction inCandida albicans

2007 ◽  
Vol 18 (3) ◽  
pp. 965-975 ◽  
Author(s):  
Francisco J. Alvarez ◽  
James B. Konopka
Keyword(s):  
Plasma Membrane ◽  
Hyphal Growth ◽  
Nutrient Sensing ◽  
Major Facilitator Superfamily ◽  
Cellular Processes ◽  
Macrophage Phagocytosis ◽  
Wide Range ◽  
High Concentrations ◽  
Hyphal Formation ◽  
Major Facilitator

The sugar N-acetylglucosamine (GlcNAc) plays an important role in nutrient sensing and cellular regulation in a wide range of organisms from bacteria to humans. In the fungal pathogen Candida albicans, GlcNAc induces a morphological transition from budding to hyphal growth. Proteomic comparison of plasma membrane proteins from buds and from hyphae induced by GlcNAc identified a novel hyphal protein (Ngt1) with similarity to the major facilitator superfamily of transporters. An Ngt1-GFP fusion was detected in the plasma membrane after induction with GlcNAc, but not other related sugars. Ngt1-GFP was also induced by macrophage phagocytosis, suggesting a role for the GlcNAc response in signaling entry into phagolysosomes. NGT1 is needed for efficient GlcNAc uptake and for the ability to induce hyphae at low GlcNAc concentrations. High concentrations of GlcNAc could bypass the need for NGT1 to induce hyphae, indicating that elevated intracellular levels of GlcNAc induce hyphal formation. Expression of NGT1 in Saccharomyces cerevisiae promoted GlcNAc uptake, indicating that Ngt1 acts directly as a GlcNAc transporter. Transport mediated by Ngt1 was specific, as other sugars could not compete for the uptake of GlcNAc. Thus, Ngt1 represents the first eukaryotic GlcNAc transporter to be discovered. The presence of NGT1 homologues in the genome sequences of a wide range of eukaryotes from yeast to mammals suggests that they may also function in the cellular processes regulated by GlcNAc, including those that underlie important diseases such as cancer and diabetes.

scholarly journals Rice Na+-Permeable Transporter OsHAK12 Mediates Shoots Na+ Exclusion in Response to Salt Stress

2021 ◽  
Vol 12 ◽  
Author(s):  
Linan Zhang ◽  
Xiangyu Sun ◽  
Yanfang Li ◽  
Xuan Luo ◽  
Shaowen Song ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Salt Stress ◽  
Salt Tolerance ◽  
Target Gene ◽  
Xylem Sap ◽  
Crop Productivity ◽  
Membrane Transporter ◽  
High Affinity ◽  
Salt Toxicity ◽  
Plasma Membrane Transporter

Soil salinity has become a major stress factor that reduces crop productivity worldwide. Sodium (Na+) toxicity in a number of crop plants is tightly linked with shoot Na+ overaccumulation, thus Na+ exclusion from shoot is crucial for salt tolerance in crops. In this study, we identified a member of the high-affinity K+ transport family (HAK), OsHAK12, which mediates shoots Na+ exclusion in response to salt stress in rice. The Oshak12 mutants showed sensitivity to salt toxicity and accumulated more Na+ in the xylem sap, leading to excessive Na+ in the shoots and less Na+ in the roots. Unlike typical HAK family transporters that transport K+, OsHAK12 is a Na+-permeable plasma membrane transporter. In addition, OsHAK12 was strongly expressed in the root vascular tissues and induced by salt stress. These findings indicate that OsHAK12 mediates Na+ exclusion from shoot, possibly by retrieving Na+ from xylem vessel thereby reducing Na+ content in the shoots. These findings provide a unique function of a rice HAK family member and provide a potential target gene for improving salt tolerance of rice.

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