A conserved GTPase-containing complex is required for intracellular sorting of the general amino-acid permease in yeast

Gao, Minggeng; Kaiser, Chris A.

doi:10.1038/ncb1419

Cited by 158 publications

(193 citation statements)

References 48 publications

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“…Moreover, the EGO-GSE complex, which, in response to amino acids, controls sorting of the general amino acid permease Gap1, and, in combination with TORC1, regulates microautophagy, resides in prevacuolar compartments (29,30). These and other studies underscore a prominent role for membranes of the protein secretory pathway as a portal for amino acid sensing and Tor-signaling events.…”

Section: Discussionmentioning

confidence: 76%

Nuclear translocation of Gln3 in response to nutrient signals requires Golgi-to-endosome trafficking in Saccharomyces cerevisiae

Puria

Zurita-Martinez

Cárdenas

2008

Proc. Natl. Acad. Sci. U.S.A.

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The yeast Saccharomyces cerevisiae has developed specialized mechanisms that enable growth on suboptimal nitrogen sources. Exposure of yeast cells to poor nitrogen sources or treatment with the Tor kinase inhibitor rapamycin elicits activation of Gln3 and transcription of nitrogen catabolite-repressed (NCR) genes whose products function in scavenging and metabolizing nitrogen. Here, we show that mutations in class C and D Vps components, which mediate Golgi-to-endosome vesicle transport, impair nuclear translocation of Gln3, NCR gene activation, and growth in poor nitrogen sources. In nutrient-replete conditions, a significant fraction of Gln3 is peripherally associated with light membranes and partially colocalizes with Vps10-containing foci. These results reveal a role for Golgi-to-endosome vesicular trafficking in TORC1-controlled nuclear translocation of Gln3 and support a model in which Tor-mediated signaling in response to nutrient cues occurs in these compartments. These findings have important implications for nutrient sensing and growth control via mTor pathways in metazoans.rapamycin action ͉ Tor signaling

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Section: Discussionmentioning

confidence: 76%

Nuclear translocation of Gln3 in response to nutrient signals requires Golgi-to-endosome trafficking in Saccharomyces cerevisiae

Puria

Zurita-Martinez

Cárdenas

2008

Proc. Natl. Acad. Sci. U.S.A.

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“…Thus, there may be some DHHC redundancy in regard to Meh1 palmitoylation. This would explain results observed by Hou et al (37) showing that membrane association of Meh1 was unchanged in akr1⌬ cells, whereas mutation of cysteines 7 and 8 produced a soluble protein (43). Neither myr-Ygl108 nor myr-Meh1 was a good substrate for Pfa3, suggesting that Pfa3 does not universally recognize SH4 domain proteins as substrates.…”

Section: Vac8 Is Palmitoylated By Pfa3 At All Three N-terminal Cysteimentioning

confidence: 78%

“…Collectively, these data support the presence of a bona fide SH4 domain in Ygl108. Meh1/Ego1/Gse2 (hereafter referred to as Meh1) is part of the EGO/GSE protein complex involved in regulating rapamycin-induced microautophagy (42) and intracellular sorting of the amino acid permease Gap1 (43). Meh1 distributes to the vacuole membrane (42,44) and endosomes (43).…”

Section: Vac8 Is Palmitoylated By Pfa3 At All Three N-terminal Cysteimentioning

confidence: 99%

Molecular Recognition of the Palmitoylation Substrate Vac8 by Its Palmitoyltransferase Pfa3

Nadolski¹,

Linder

2009

Journal of Biological Chemistry

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Palmitoylation of the yeast vacuolar protein Vac8 is important for its role in membrane-mediated events such as vacuole fusion. It has been established both in vivo and in vitro that Vac8 is palmitoylated by the Asp-His-His-Cys (DHHC) protein Pfa3. However, the determinants of Vac8 critical for recognition by Pfa3 have yet to be elucidated. This is of particular importance because of the lack of a consensus sequence for palmitoylation. Here we show that Pfa3 was capable of palmitoylating each of the three N-terminal cysteines of Vac8 and that this reaction was most efficient when Vac8 is N-myristoylated. Additionally, when we analyzed the Src homology 4 (SH4) domain of Vac8 independent of the rest of the protein, palmitoylation by Pfa3 still occurred. However, the specificity of palmitoylation seen for the full-length protein was lost, and the SH4 domain was palmitoylated by all five of the yeast DHHC proteins tested. These data suggested that a region of the protein C-terminal to the SH4 domain was important for conferring specificity of palmitoylation. This was confirmed by use of a chimeric protein in which the SH4 domain of Vac8 was swapped for that of Meh1, another palmitoylated and N-myristoylated protein in yeast. In this case we saw specificity mimic that of wild type Vac8. Competition experiments revealed that the 11th armadillo repeat of Vac8 is an important element for recognition by Pfa3. This demonstrates that regions distant from the palmitoylated cysteines are important for recognition by DHHC proteins.S-Palmitoylation (hereafter referred to as palmitoylation) is a widespread post-translational modification in which the fatty acid palmitate (16:0) is attached to a cysteine residue via a thioester linkage. Palmitate can be released from a cysteine by hydrolysis of the thioester linkage; thus palmitoylation is a reversible modification. Numerous eukaryotic proteins are palmitoylated, and substrates include both peripheral and transmembrane domain proteins. The functional consequences of palmitoylation are diverse. Membrane association, protein stability, and protein trafficking are among the properties that can be modulated by the palmitoylation status of a protein (reviewed in 1, 2).The enzymes responsible for palmitoylation have only recently been identified. The first protein acyltransferases (PATs) 3 discovered were Erf2 and Akr1 in yeast, which palmitoylate Ras2 and Yck2, respectively (3, 4). Both Erf2 and Akr1 are transmembrane proteins with an Asp-His-(His/Tyr)-Cys (DHHC) motif embedded in a cysteine-rich domain (CRD). Homology with this domain has identified five additional DHHC proteins in Saccharomyces cerevisiae. These seven proteins account for the bulk of palmitoylating activity in the cell (5).To date 23 DHHC proteins have been identified in mammals (6). As the field has progressed DHHC proteins have been linked to the regulation of neurotransmission (7-9), nitric oxide release (10), and cell-cell contacts (11). Palmitoylation of Huntingtin by HIP14 (DHHC17) plays a protective role in ...

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“…In this context, the vacuolar membrane-associated EGO (exit from rapamycin-induced growth arrest) protein complex (EGOC) , which consists of Ego1/Meh1/Gse2, Ego3/Nir1/Slm4/Gse1, Gtr1, and Gtr2, has been proposed to function as a critical hub that directly relays an amino acid signal to TORC1 (De Virgilio and Loewith 2006a, b;Gao and Kaiser 2006;Piper 2006). This initial idea has recently been bolstered by the finding that the EGOC subunit Gtr1, which is homologous to mammalian Rag GTPases, directly interacts with and activates TORC1 in an amino acid-sensitive and nucleotide-dependent manner (Binda et al 2009).…”

Section: How Is Tor Signalling Regulated?mentioning

confidence: 99%

Life in the midst of scarcity: adaptations to nutrient availability in Saccharomyces cerevisiae

et al. 2010

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Cells of all living organisms contain complex signal transduction networks to ensure that a wide range of physiological properties are properly adapted to the environmental conditions. The fundamental concepts and individual building blocks of these signalling networks are generally well-conserved from yeast to man; yet, the central role that growth factors and hormones play in the regulation of signalling cascades in higher eukaryotes is executed by nutrients in yeast. Several nutrient-controlled pathways, which regulate cell growth and proliferation, metabolism and stress resistance, have been defined in yeast. These pathways are integrated into a signalling network, which ensures that yeast cells enter a quiescent, resting phase (G 0 ) to survive periods of nutrient scarceness and that they rapidly resume growth and cell proliferation when nutrient conditions become favourable again. A series of well-conserved nutrient-sensory protein kinases perform key roles in this signalling network: i.e. Snf1, PKA, Tor1 and Tor2, Sch9 and Pho85-Pho80. In this review, we provide a comprehensive overview on the current understanding of the signalling processes mediated via these kinases with a particular focus on how these individual pathways converge to signalling networks that ultimately ensure the dynamic translation of extracellular nutrient signals into appropriate physiological responses.

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A conserved GTPase-containing complex is required for intracellular sorting of the general amino-acid permease in yeast

Cited by 158 publications

References 48 publications

Nuclear translocation of Gln3 in response to nutrient signals requires Golgi-to-endosome trafficking in Saccharomyces cerevisiae

Nuclear translocation of Gln3 in response to nutrient signals requires Golgi-to-endosome trafficking in Saccharomyces cerevisiae

Molecular Recognition of the Palmitoylation Substrate Vac8 by Its Palmitoyltransferase Pfa3

Life in the midst of scarcity: adaptations to nutrient availability in Saccharomyces cerevisiae

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