The trehalose pathway and intracellular glucose phosphates as modulators of potassium transport and general cation homeostasis in yeast

Mulet, José; Alejandro, Santiago; Romero, Carlos; Serrano, Ramón

doi:10.1002/yea.1126

Cited by 22 publications

(13 citation statements)

References 42 publications

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“…role in salt and pH tolerance in yeast through regulating the trafficking of the potassium transporters Trk1p and Trk2p (47,52). CKII is involved in multiple processes, including the cell cycle, cell polarization, and transcription regulation (53).…”

Section: S 251amentioning

confidence: 99%

Negative Regulation of the Yeast ABC Transporter Ycf1p by Phosphorylation within Its N-terminal Extension

Paumi¹,

Chuk

Chevelev

et al. 2008

Journal of Biological Chemistry

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The yeast vacuolar membrane protein Ycf1p and its mammalian counterpart, MRP1, belong to the ABCC subfamily of ATPbinding cassette (ABC) transporters that rid cells of toxic endogenous and xenobiotic compounds. Like most members of the ABCC subfamily, Ycf1p contains an N-terminal extension in addition to its ABC "core" domain and transports substrates in the form of glutathione conjugates. Ycf1p is subject to complex regulation to ensure its optimal function. Previous studies showed that Ycf1p activity is stimulated by a guanine nucleotide exchange factor, Tus1p, and is positively regulated by phosphorylation in its ABC core domain at residues Ser-908 and Thr-911. Here we provide evidence that phosphorylation of Ser-251 in the Ycf1p N-terminal extension negatively regulates activity. Mutant Ycf1p-S251A exhibits increased resistance to cadmium in vivo and increased Ycf1p-dependent transport of [ 3 H]estradiol-␤-17-glucuronide in vitro as compared with wild-type Ycf1p. Activity is restored to the wild-type level for Ycf1-S251E. To identify kinase(s) that negatively regulate Ycf1p function, we conducted an integrated membrane yeast two-hybrid (iMYTH) screen and identified two kinase genes, CKA1 and HAL5, deletion of which increases Ycf1p function. Genetic evidence suggests that Cka1p may regulate Ycf1p function through phosphorylation of Ser-251 either directly or indirectly. Overall, this study provides compelling evidence that negative, as well as positive, regulation of Ycf1p is mediated by phosphorylation.

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Section: S 251amentioning

confidence: 99%

Negative Regulation of the Yeast ABC Transporter Ycf1p by Phosphorylation within Its N-terminal Extension

Paumi¹,

Chuk

Chevelev

et al. 2008

Journal of Biological Chemistry

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“…However, the downstream signaling targets that modulate vacuolar Ca 2ϩ uptake remain to be identified. In a recent study, Mulet and coworkers (30) reported that trehalose 6-phosphate synthase (TPS)1 activity alters the ion transport characteristics of the K ϩ channels TRK1 and TRK2 through the modulation of cellular Glc phosphate levels. They also noted that like TPS1, PGM and hexokinase 2 are also capable of altering the levels of Glc phosphates and that elevated Glc phosphate levels activate TRK by way of the calcineurin pathway (30).…”

Section: LImentioning

confidence: 99%

Inhibition of phosphoglucomutase activity by lithium alters cellular calcium homeostasis and signaling in Saccharomyces cerevisiae

Csutora¹,

Strassz²,

Boldizsár³

et al. 2005

American Journal of Physiology-Cell Physiology

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“…Paromomycin and rapamycin were added at the indicated concentration from a concentrated stock to autoclaved yeast extract/peptone/dextrose with 2% agar prior to gelation. Spot tests of yeast growth were performed as described previously (23), but plates were incubated at a restrictive temperature (37°C) for the thermosensitive allele of TOR2. Immunoprecipitation assays were performed as described previously (24).…”

Section: Methodsmentioning

confidence: 99%

The Solution Structure of the FATC Domain of the Protein Kinase Target of Rapamycin Suggests a Role for Redox-dependent Structural and Cellular Stability

Dames¹,

Mulet

Rathgeb-Szabo³

et al. 2005

Journal of Biological Chemistry

116

159

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The target of rapamycin (TOR) is a highly conserved Ser/Thr kinase that plays a central role in the control of cellular growth. TOR has a characteristic multidomain structure. Only the kinase domain has catalytic function; the other domains are assumed to mediate interactions with TOR substrates and regulators. Except for the rapamycin-binding domain, there are no high-resolution structural data available for TOR. Here, we present a structural, biophysical, and mutagenesis study of the extremely conserved COOH-terminal FATC domain. The importance of this domain for TOR function has been highlighted in several publications. We show that the FATC domain, in its oxidized form, exhibits a novel structural motif consisting of an ␣-helix and a COOHterminal disulfide-bonded loop between two completely conserved cysteine residues. Upon reduction, the flexibility of the loop region increases dramatically. The structural data, the redox potential of the disulfide bridge, and the biochemical data of a cysteine to serine mutant indicate that the intracellular redox potential can affect the cellular amount of the TOR protein via the FATC domain. Because the amount of TOR mRNA is not changed, the redox state of the FATC disulfide bond is probably influencing the degradation of TOR.Regulation of cellular growth is a prerequisite for cells, organs, and organisms to achieve a characteristic size. The target of rapamycin (TOR, 1 also known as FRAP, RAFT, RAPT, or SEPT) is a highly conserved 280-kDa Ser/Thr kinase that has been shown to play a central role in the control of cell growth in organisms ranging from yeast to human (1, 2). TOR proteins consist of several functional domains (see Fig. 1a) (3). The amino-terminal ϳ1200 residues consist of stretches of HEAT (huntingtin, elongation factor 3, regulatory subunit A of PP2A, TOR1) repeats, which typically mediate protein-protein interactions. Recently, it was also suggested that the ϳ550-amino acid-long FAT (FRAP, ATM, TTRAP) domain that follows the HEAT repeats is composed of HEAT repeat-like ␣-helical structures and could also serve as a protein interaction platform (4). The known interactions of TOR with other proteins have been reviewed recently (1, 2). The FKBP12-rapamycin binding site is flanked by the FAT domain and the catalytic kinase domain. Binding of the FKBP12⅐rapamycin complex to the FKBP12-rapamycin-binding domain specifically inhibits TOR (5). The catalytic kinase domain is highly homologous to that of phosphatidylinositol 3-and 4-kinases. Thus, TOR and its relatives have been termed phosphatidylinositol kinase-related kinases. TOR has been shown to fulfill its functions by directly phosphorylating serine and threonine residues of target proteins and by regulating protein phosphatases (1, 2). The carboxylterminal ϳ33 residues of TOR form the FATC domain. In all phosphatidylinositol kinase-related kinases, the FATC domain always occurs in tandem with the FAT domain (6). Previous studies have shown that the FATC domain is indispensable for TOR function in vivo and ...

show abstract

The trehalose pathway and intracellular glucose phosphates as modulators of potassium transport and general cation homeostasis in yeast

Cited by 22 publications

References 42 publications

Negative Regulation of the Yeast ABC Transporter Ycf1p by Phosphorylation within Its N-terminal Extension

Negative Regulation of the Yeast ABC Transporter Ycf1p by Phosphorylation within Its N-terminal Extension

Inhibition of phosphoglucomutase activity by lithium alters cellular calcium homeostasis and signaling in Saccharomyces cerevisiae

The Solution Structure of the FATC Domain of the Protein Kinase Target of Rapamycin Suggests a Role for Redox-dependent Structural and Cellular Stability

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