The Study of Methionine Uptake inSaccharomyces cerevisiaeReveals a New Family of Amino Acid Permeases

Isnard, Anne‐Dominique; Thomas, Dominique; Surdin-Kerjan, Yolande

doi:10.1006/jmbi.1996.0529

Cited by 112 publications

(98 citation statements)

References 26 publications

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“…In the presence of methionine, weak (about 2-fold) repression of sulfate transport occurred (4) so tubercle bacteria would take up methionine 5-6ϫ faster than sulfate at the estimated physiological concentration. Although the genes that encode the methionine transporter were not identified (2), there are candidates among the many predicted ABC transporters for amino acid, including methionine, transport (37)(38)(39).…”

Section: Discussionmentioning

confidence: 99%

Functional Demonstration of Reverse Transsulfuration in the Mycobacterium tuberculosis Complex Reveals That Methionine Is the Preferred Sulfur Source for Pathogenic Mycobacteria

Wheeler

Coldham

Keating

et al. 2005

Journal of Biological Chemistry

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Methionine can be used as the sole sulfur source by the Mycobacterium tuberculosis complex although it is not obvious from examination of the genome annotation how these bacteria utilize methionine. Given that genome annotation is a largely predictive process, key challenges are to validate these predictions and to fill in gaps for known functions for which genes have not been annotated. We have addressed these issues by functional analysis of methionine metabolism. Transport, followed by metabolism of 35 S methionine into the cysteine adduct mycothiol, demonstrated the conversion of exogenous methionine to cysteine. Mutational analysis and cloning of the Rv1079 gene showed it to encode the key enzyme required for this conversion, cystathionine ␥-lyase (CGL). Rv1079, annotated metB, was predicted to encode cystathionine ␥-synthase (CGS), but demonstration of a ␥-elimination reaction with cystathionine as well as the ␥-replacement reaction yielding cystathionine showed it encodes a bifunctional CGL/CGS enzyme. Consistent with this, a Rv1079 mutant could not incorporate sulfur from methionine into cysteine, while a cysA mutant lacking sulfate transport and a methionine auxotroph was hypersensitive to the CGL inhibitor propargylglycine. Thus, reverse transsulfuration alone, without any sulfur recycling reactions, allows M.tuberculosis to use methionine as the sole sulfur source. Intracellular cysteine was undetectable so only the CGL reaction occurs in intact mycobacteria. Cysteine desulfhydrase, an activity we showed to be separable from CGL/CGS, may have a role in removing excess cysteine and could explain the ability of M. tuberculosis to recycle sulfur from cysteine, but not methionine.

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Section: Discussionmentioning

confidence: 99%

Functional Demonstration of Reverse Transsulfuration in the Mycobacterium tuberculosis Complex Reveals That Methionine Is the Preferred Sulfur Source for Pathogenic Mycobacteria

Wheeler

Coldham

Keating

et al. 2005

Journal of Biological Chemistry

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“…It was previously reported that methionine is transported in yeast cells by at least three different permeases: the high-affinity permease (K m ϭ 0.013 mM) encoded by the MUP1 gene, a low-affinity permease (K m ϭ 0.2 mM) whose gene (MUP2) remained uncharacterized, and a very-low-affinity permease (K m ϭ 1 mM) encoded by the MUP3 gene (38). The lowaffinity permease is probably Agp1p: its activity was measured under growth conditions leading to the induction of AGP1, it displays a broad specificity range, and methionine transport mediated by this permease is inhibited by leucine with an apparent K i value (0.30 mM) (38) very close to the K m value of Agp1 for leucine.…”

Section: Discussionmentioning

confidence: 99%

“…Some previously characterized genes, such as MUP1 and MUP3 (38), TAT1 and TAT2 (9,75), and GNP1 (90), were also included in this analysis because the reported experiments on expression of these genes were carried out in complex medium or in minimal medium containing amino acids to compensate for amino acid auxotrophies, i.e., under conditions where the expression of Ssy1p-responsive genes should appear constitutive. In the RT-PCR experiments (Fig.…”

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confidence: 99%

Amino Acid Signaling in Saccharomyces cerevisiae: a Permease-Like Sensor of External Amino Acids and F-Box Protein Grr1p Are Required for Transcriptional Induction of the AGP1 Gene, Which Encodes a Broad-Specificity Amino Acid Permease

Iraqui

Vissers

Bernard

et al. 1999

Molecular and Cellular Biology

243

308

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The SSY1 gene of Saccharomyces cerevisiae encodes a member of a large family of amino acid permeases. Compared to the 17 other proteins of this family, however, Ssy1p displays unusual structural features reminiscent of those distinguishing the Snf3p and Rgt2p glucose sensors from the other proteins of the sugar transporter family. We show here that SSY1 is required for transcriptional induction, in response to multiple amino acids, of the AGP1 gene encoding a low-affinity, broad-specificity amino acid permease. Total noninduction of the AGP1 gene in the ssy1⌬ mutant is not due to impaired incorporation of inducing amino acids. Conversely, AGP1 is strongly induced by tryptophan in a mutant strain largely deficient in tryptophan uptake, but it remains unexpressed in a mutant that accumulates high levels of tryptophan endogenously. Induction of AGP1 requires Uga35p(Dal81p/DurLp), a transcription factor of the Cys 6 -Zn 2 family previously shown to participate in several nitrogen induction pathways. Induction of AGP1 by amino acids also requires Grr1p, the F-box protein of the SCF Grr1 ubiquitin-protein ligase complex also required for transduction of the glucose signal generated by the Snf3p and Rgt2p glucose sensors. Systematic analysis of amino acid permease genes showed that Ssy1p is involved in transcriptional induction of at least five genes in addition to AGP1. Our results show that the amino acid permease homologue Ssy1p is a sensor of external amino acids, coupling availability of amino acids to transcriptional events. The essential role of Grr1p in this amino acid signaling pathway lends further support to the hypothesis that this protein participates in integrating nutrient availability with the cell cycle.

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“…The three putative methionine permeases show significant homology to MUP1 of S. cerevisiae, which encodes a high-affinity methionine permease (366). Available data from studies of S. cerevisiae suggest that MUP1 is also involved in cysteine uptake (429).…”

Section: Sulfur Metabolismmentioning

confidence: 99%

Lessons from the Genome Sequence ofNeurospora crassa: Tracing the Path from Genomic Blueprint to Multicellular Organism

Borkovich

Alex

Yarden

et al. 2004

Microbiol Mol Biol Rev

595

618

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We present an analysis of over 1,100 of the ∼10,000 predicted proteins encoded by the genome sequence of the filamentous fungus Neurospora crassa. Seven major areas of Neurospora genomics and biology are covered. First, the basic features of the genome, including the automated assembly, gene calls, and global gene analyses are summarized. The second section covers components of the centromere and kinetochore complexes, chromatin assembly and modification, and transcription and translation initiation factors. The third area discusses genome defense mechanisms, including repeat induced point mutation, quelling and meiotic silencing, and DNA repair and recombination. In the fourth section, topics relevant to metabolism and transport include extracellular digestion; membrane transporters; aspects of carbon, sulfur, nitrogen, and lipid metabolism; the mitochondrion and energy metabolism; the proteasome; and protein glycosylation, secretion, and endocytosis. Environmental sensing is the focus of the fifth section with a treatment of two-component systems; GTP-binding proteins; mitogen-activated protein, p21-activated, and germinal center kinases; calcium signaling; protein phosphatases; photobiology; circadian rhythms; and heat shock and stress responses. The sixth area of analysis is growth and development; it encompasses cell wall synthesis, proteins important for hyphal polarity, cytoskeletal components, the cyclin/cyclin-dependent kinase machinery, macroconidiation, meiosis, and the sexual cycle. The seventh section covers topics relevant to animal and plant pathogenesis and human disease. The results demonstrate that a large proportion of Neurospora genes do not have homologues in the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe. The group of unshared genes includes potential new targets for antifungals as well as loci implicated in human and plant physiology and disease

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The Study of Methionine Uptake inSaccharomyces cerevisiaeReveals a New Family of Amino Acid Permeases

Cited by 112 publications

References 26 publications

Functional Demonstration of Reverse Transsulfuration in the Mycobacterium tuberculosis Complex Reveals That Methionine Is the Preferred Sulfur Source for Pathogenic Mycobacteria

Functional Demonstration of Reverse Transsulfuration in the Mycobacterium tuberculosis Complex Reveals That Methionine Is the Preferred Sulfur Source for Pathogenic Mycobacteria

Amino Acid Signaling in Saccharomyces cerevisiae: a Permease-Like Sensor of External Amino Acids and F-Box Protein Grr1p Are Required for Transcriptional Induction of the AGP1 Gene, Which Encodes a Broad-Specificity Amino Acid Permease

Lessons from the Genome Sequence ofNeurospora crassa: Tracing the Path from Genomic Blueprint to Multicellular Organism

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