A second nitrogen permease regulator in <i>Saccharomyces cerevisiae</i>

Rousselet, Germain; Simon, Matthieu; Ripoche, Pierre; Buhler, Jean‐Marie

doi:10.1016/0014-5793(95)00038-b

Cited by 24 publications

(36 citation statements)

References 19 publications

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“…1). These results indicate that DUR3 and SAM3 are involved in polyamine transport, presumably functioning directly as polyamine transporters, although DUR3 and SAM3 have been reported to be an urea and an S-adenosylmethionine transporter, respectively (22,33).…”

Section: Resultsmentioning

confidence: 86%

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Polyamine Uptake by DUR3 and SAM3 in Saccharomyces cerevisiae

Uemura

Kashiwagi

Igarashi

2007

Journal of Biological Chemistry

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It has been reported that GAP1 and AGP2 catalyze the uptake of polyamines together with amino acids in Saccharomyces cerevisiae. We have looked for polyamine-preferential uptake proteins in S. cerevisiae. DUR3 catalyzed the uptake of polyamines together with urea, and SAM3 was found to catalyze the uptake of polyamines together with S-adenosylmethionine, glutamic acid, and lysine. Polyamine uptake was greatly decreased in both DUR3-and SAM3-deficient cells. The K m values for putrescine and spermidine of DUR3 were 479 and 21.2 M, respectively, and those of SAM3 were 433 and 20.7 M, respectively. Polyamine stimulation of cell growth of a polyamine requiring mutant, which is deficient in ornithine decarboxylase, was not influenced by the disruption of GAP1 and AGP2, but it was diminished by the disruption of DUR3 and SAM3. Furthermore, the polyamine stimulation of cell growth of a polyamine-requiring mutant was completely inhibited by the disruption of both DUR3 and SAM3. The results indicate that DUR3 and SAM3 are major polyamine uptake proteins in yeast. We previously reported that polyamine transport protein kinase 2 regulates polyamine transport. It was found that DUR3 (but not SAM3) was activated by phosphorylation of Thr 250 , Ser 251 , and Thr 684 by polyamine transport protein kinase 2.Polyamines (putrescine, spermidine, and spermine) in cells, which are essential for cell growth, are regulated by biosynthesis, degradation, and transport (1-4). With regard to polyamine transport, the properties of four polyamine transport systems were characterized in Escherichia coli (5-8). They include spermidine-preferential and putrescine-specific uptake systems as well as PotE (involved in the excretion of putrescine by a putrescine-ornithine antiporter activity) and CadB (involved in the excretion of cadaverine by a cadaverine-lysine antiporter activity). The former two transport systems function at neutral pH (2), whereas the latter two transport systems at acidic pH (9). In Saccharomyces cerevisiae, we identified four genes that encode polyamine excretion proteins TPO1-TPO4, mainly located on the plasma membrane (10 -12). We also found that UGA4 (located on vacuoles) can catalyze the uptake of ␥-aminobutyric acid and putrescine (13), and TPO5 (located on Golgi or post-Golgi secretory vesicles) can catalyze the excretion of polyamines (14). Furthermore, we reported that GAP1, located on the plasma membrane, can catalyze the uptake of putrescine and spermidine together with the uptake of amino acids (15). Although it has been reported that AGP2 can selectively catalyze the uptake of spermidine (16), there is also a report that AGP2 functions as an amino acid permease (17). In this study, we looked for proteins that can preferentially catalyze the uptake of polyamines in S. cerevisiae. We found that DUR3 can catalyze the uptake of polyamines together with urea, and SAM3 (which belongs to the family of amino acid polyamine-organocation transporters (18)) can catalyze the uptake of putrescine and spermidine together wit...

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Section: Resultsmentioning

confidence: 86%

“…Thus, we tried to identify polyamine-preferential transporters and found that DUR3 and SAM3 are polyaminepreferential transporters. DUR3 and SAM3 were originally reported as transporters for urea and S-adenosylmethionine (19,33). However, normally urea and S-adenosylmethionine do not exist at high levels outside cells.…”

Section: Discussionmentioning

confidence: 99%

Polyamine Uptake by DUR3 and SAM3 in Saccharomyces cerevisiae

Uemura

Kashiwagi

Igarashi

2007

Journal of Biological Chemistry

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“…First, ScNpr2p, but not SpNpr2, contains two characteristic PEST sequences, which are preferentially found in rapidly degraded regulatory proteins (Rousselet et al 1995). Second, in budding yeast, deletion of ScNpr2p did not display rapamycin sensitivity (Wu and Tu 2011), whereas in fission yeast deletion of SpNpr2 resulted in rapamycin sensitivity.…”

Section: Fission Yeast Npr2 and Budding Yeast Npr2p Have Similar But mentioning

confidence: 99%

“…In budding yeast, Npr2p was first isolated as a nitrogen permeases regulatory protein (Rousselet et al 1995), and recently Npr2p was demonstrated to be a subunit of Npr2-Npr3 (Neklesa and Davis 2009), Iml1p-Npr2p-Npr3p (Wu and Tu 2011), and SEA (Sea1p/Imh1p-Sea2p-Sea3p-Sea4p-Npr2p-Npr3p) complexes (Dokudovskaya et al 2011). The Npr2-Npr3 complex was identified in a genome-wide screen as negative regulators of TORC1 complex (Neklesa and Davis 2009).…”

Section: Fission Yeast Npr2 and Budding Yeast Npr2p Have Similar But mentioning

confidence: 99%

TORC1 Signaling Is Governed by Two Negative Regulators in Fission Yeast

Liu

Zhang

et al. 2013

Genetics

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The target of rapamycin (TOR) is a highly conserved protein kinase that regulates cell growth and metabolism. Here we performed a genome-wide screen to identify negative regulators of TOR complex 1 (TORC1) in Schizosaccharomyces pombe by isolating mutants that phenocopy Dtsc2, in which TORC1 signaling is known to be up-regulated. We discovered that Dnpr2 displayed similar phenotypes to Dtsc2 in terms of amino acid uptake defects and mislocalization of the Cat1 permease. However, Dnpr2 and Dtsc2 clearly showed different phenotypes in terms of rapamycin supersensitivity and Isp5 transcription upon various treatments. Furthermore, we showed that Tor2 controls amino acid homeostasis at the transcriptional and post-transcriptional levels. Our data reveal that both Npr2 and Tsc2 negatively regulate TORC1 signaling, and Npr2, but not Tsc2, may be involved in the feedback loop of a nutrient-sensing pathway.T HE target of rapamycin (TOR) plays vitally important roles in regulating cell growth and metabolism. TOR interacts with several proteins to form two structurally and functionally distinct complexes named TOR complex 1 (TORC1) and 2 (TORC2) Sabatini 2009, 2012). In response to environmental cues, TORC1 controls cell growth and differentiation by coordinating diverse cellular processes including transcription, translation, and autophagy. Research on TORC1 has generated a model of the complex TOR signaling network (Huang and Manning 2009;Orlova and Crino 2010;Laplante and Sabatini 2012). In the regulation of TORC1 signaling, four major signals have been identified, namely growth factors (insulin, IGF, etc.), energy status (AMP/ATP ratio), oxygen levels, and nutrients (amino acids) Sabatini 2009, 2012). In mammals, the tuberous sclerosis complex 1 and 2 (TSC1-TSC2) serves as a key point of signal integration. The growth factors stimulate TORC1 signaling via PI3K-Akt/ PKB-mediated phosphoinhibition of TSC2 (Inoki et al. 2002;Manning et al. 2002). The energy starvation inhibits TORC1 signaling via AMPK-dependent phosphoactivation of TSC2 (Inoki et al. 2003). Then, TSC2 negatively regulates TORC1 activity by converting GTP-bound Rheb (Ras homolog enriched in brain) into its inactive GDP-bound state (Inoki et al. 2003;Tee et al. 2003). The amino acids, in particular the branched-chain amino acid leucine, positively regulate TORC1. The TORC1 signaling remains sensitive to amino acid deprivation in TSC2 2/2 cells (Nobukuni et al. 2005), indicating that the activation of TORC1 by amino acids is independent of TSC2. Recently, it was demonstrated that TORC1 responds to amino acid availability via mechanisms involving Rag GTPases (Sancak et al. 2008). In the presence of amino acids, the Rag GTPases interact with TORC1, thereby promoting the translocation of TORC1 to the lysosomal membranes and facilitating Rheb's activation of TORC1 (Sancak et al. 2010).In budding yeast Saccharomyces cerevisiae, TOR1 and TOR2 genes were originally identified as the targets of rapamycin, and mutations in TOR1 or TOR2 genes confer resi...

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“…urea, proline) (Ljungdahl and Daignan-Fornier, 2012). The SEACIT component Npr2, which stands for nitrogen permease regulator 2, was originally identified as a protein necessary for yeast growth in poor nitrogen sources (Rousselet et al, 1995). In turn, Npr3 was described as a protein required for sporulation -a 'hard times coming' response that is initiated by the depletion of multiple factors, including nitrogen (Enyenihi and Saunders, 2003).…”

Section: Modulation Of Nitrogen Metabolism By the Sea Complexmentioning

confidence: 99%

SEA you later alli-GATOR – a dynamic regulator of the TORC1 stress response pathway

Dokudovskaya

Rout

2015

Journal of Cell Science

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Cells constantly adapt to various environmental changes and stresses. The way in which nutrient and stress levels in a cell feed back to control metabolism and growth are, unsurprisingly, extremely complex, as responding with great sensitivity and speed to the 'feast or famine, slack or stress' status of its environment is a central goal for any organism. The highly conserved target of rapamycin complex 1 (TORC1) controls eukaryotic cell growth and response to a variety of signals, including nutrients, hormones and stresses, and plays the key role in the regulation of autophagy. A lot of attention has been paid recently to the factors in this pathway functioning upstream of TORC1. In this Commentary, we focus on a major, newly discovered upstream regulator of TORC1 -the multiprotein SEA complex, also known as GATOR. We describe the structural and functional features of the yeast complex and its mammalian homolog, and their involvement in the regulation of the TORC1 pathway and TORC1-independent processes. We will also provide an overview of the consequences of GATOR deregulation in cancer and other diseases.

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A second nitrogen permease regulator in Saccharomyces cerevisiae

Cited by 24 publications

References 19 publications

Polyamine Uptake by DUR3 and SAM3 in Saccharomyces cerevisiae

Polyamine Uptake by DUR3 and SAM3 in Saccharomyces cerevisiae

TORC1 Signaling Is Governed by Two Negative Regulators in Fission Yeast

SEA you later alli-GATOR – a dynamic regulator of the TORC1 stress response pathway

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