Crossref journal-article
Oxford University Press (OUP)
Genetics (286)
Abstract

Abstract Ssy1p and Ptr3p are components of the yeast plasma membrane SPS amino acid sensor. In response to extracellular amino acids this sensor initiates metabolic signals that ultimately regulate the functional expression of several amino acid-metabolizing enzymes and amino acid permeases (AAPs). As a result of diminished leucine uptake capabilities, ssy1Δ leu2 and ptr3Δ leu2 mutant strains are unable to grow on synthetic complete medium (SC). Genes affecting the functional expression of AAPs were identified by selecting spontaneous suppressing mutations in amino acid sensor-independent (ASI) genes that restore growth on SC. The suppressors define 11 recessive (asi) complementation groups and 5 dominant (ASI) linkage groups. Strains with mutations in genes assigned to these 16 groups fall into two phenotypic classes. Mutations in the class I genes (ASI1, ASI2, ASI3, TUP1, SSN6, ASI13) derepress the transcription of AAP genes. ASI1, ASI2, and ASI3 encode novel membrane proteins, and Asi1p and Asi3p are homologous proteins that have conserved ubiquitin ligase-like RING domains at their extreme C termini. Several of the class II genes (DOA4, UBA1, BRO1, BUL1, RSP5, VPS20, VPS36) encode proteins implicated in controlling aspects of post-Golgi endosomal-vacuolar protein sorting. The results from genetic and phenotypic analysis indicate that SPS sensor-initiated signals function positively to facilitate amino acid uptake and that two independent ubiquitin-mediated processes negatively modulate amino acid uptake.

Bibliography

Forsberg, H., Hammar, M., Andréasson, C., Molinér, A., & Ljungdahl, P. O. (2001). Suppressors of ssy1 and ptr3 Null Mutations Define Novel Amino Acid Sensor-Independent Genes in Saccharomyces cerevisiae. Genetics, 158(3), 973–988.

Authors 5
  1. Hanna Forsberg (first)
  2. Mårten Hammar (additional)
  3. Claes Andréasson (additional)
  4. Annalena Molinér (additional)
  5. Per O Ljungdahl (additional)
References 76 Referenced 71
  1. 10.1111/j.1365-2958.1995.tb02237.x / Mol. Microbiol. / A recognition component of the ubiquitin system is required for peptide transport in Saccharomyces cerevisiae by Alagramam (1995)
  2. 10.1002/yea.320101003 / Yeast / A family of vectors that facilitate transposon and insertional mutagenesis of cloned genes in yeast by Allen (1994)
  3. 10.1091/mbc.3.6.633 / Mol. Biol. Cell / The yeast Ca2+-ATPase homologue, PMR1, is required for normal Golgi function and localizes in a novel Golgi-like distribution by Antebi (1992)
  4. {'key': '2022010506122149700_R4', 'first-page': '43', 'article-title': 'G1 cyclin degradation and cell differentiation in Saccharomyces cerevisiae', 'volume': '318', 'author': 'Barral', 'year': '1995', 'journal-title': 'C. R. Acad. Sci. III'} / C. R. Acad. Sci. III / G1 cyclin degradation and cell differentiation in Saccharomyces cerevisiae by Barral (1995)
  5. 10.1038/35050524 / Nat. Cell Biol. / Hrd1p/Der3p is a membrane-anchored ubiquitin ligase required for ER-associated degradation by Bays (2001)
  6. 10.1083/jcb.146.6.1227 / J. Cell Biol. / Starvation induces vacuolar targeting and degradation of the tryptophan permease in yeast by Beck (1999)
  7. 10.1091/mbc.9.1.209 / Mol. Biol. Cell / Der3p/Hrd1p is required for endoplasmic reticulum-associated degradation of misfolded lumenal and integral membrane proteins by Bordallo (1998)
  8. 10.1093/emboj/17.1.269 / EMBO J. / The N-end rule pathway controls the import of peptides through degradation of a transcriptional repressor by Byrd (1998)
  9. {'key': '2022010506122149700_R9', 'volume-title': 'Yeast, a Practical Approach', 'author': 'Campell', 'year': '1988'} / Yeast, a Practical Approach by Campell (1988)
  10. 10.1016/0378-1119(92)90454-W / Gene / Multifunctional yeast high-copy-number shuttle vectors by Christianson (1992)
  11. 10.1016/S0092-8674(00)80099-9 / Cell / Budding yeast SKP1 encodes an evolutionarily conserved kinetichore protein required for cell cycle progression by Connelly (1996)
  12. 10.1046/j.1365-2958.1998.01094.x / Mol. Microbiol. / Regulation of expression of the amino acid transporter gene BAP3 in Saccharomyces cerevisiae by de Boer (1998)
  13. 10.1093/nar/28.4.974 / Nucleic Acids Res. / Stp1p, Stp2p and Abf1p are involved in regulation of expression of the amino acid transporter gene BAP3 of Saccharomyces cerevisiae by de Boer (2000)
  14. 10.1046/j.1365-2958.1998.00714.x / Mol. Microbiol. / The permease homologue Ssy1p controls the expression of amino acid and peptide transporter genes in Saccharomyces cerevisiae by Didion (1998)
  15. 10.1083/jcb.145.6.1199 / J. Cell Biol. / A role for ubiquitination in mitochondrial inheritance in Saccharomyces cerevisiae by Fisk (1999)
  16. 10.1128/MCB.21.3.814-826.2001 / Mol. Cell. Biol. / Genetic and biochemical analysis of the yeast plasma membrane Ssy1p-Ptr3p-Ssy5p sensor of extracellular amino acids by Forsberg (2001)
  17. 10.1111/j.1749-6632.1993.tb32280.x / Ann. NY Acad. Sci. / The RING finger. A novel protein sequence motif related to the zinc finger by Freemont (1993)
  18. 10.1016/S0960-9822(00)00287-6 / Curr. Biol. / RING for destruction? by Freemont (2000)
  19. 10.1074/jbc.271.18.10946 / J. Biol. Chem. / Ubiquitination mediated by the Npi1p/Rsp5p ubiquitin-protein ligase is required for endocytosis of the yeast uracil permease by Galan (1996)
  20. 10.1042/bj3460329 / Biochem. J. / Zinc-regulated ubiquitin conjugation signals endocytosis of the yeast ZRT1 zinc transporter by Gitan (2000)
  21. 10.1093/nar/24.13.2519 / Nucleic Acids Res. / A new efficient gene disruption cassette for repeated use in budding yeast by Guldener (1996)
  22. {'key': '2022010506122149700_R22', 'volume-title': 'Guide to Yeast Genetics and Molecular Biology', 'author': 'Guthrie', 'year': '1991'} / Guide to Yeast Genetics and Molecular Biology by Guthrie (1991)
  23. 10.1073/pnas.86.15.5786 / Proc. Natl. Acad. Sci. USA / Predicting the orientation of eukaryotic membrane-spanning proteins by Hartmann (1989)
  24. 10.1111/j.1365-2958.1995.mmi_18010077.x / Mol. Microbiol. / NPl1, an essential yeast gene involved in induced degradation of Gap1 and Fur4 permeases, encodes the Rsp5 ubiquitin-protein ligase by Hein (1995)
  25. 10.1083/jcb.153.4.649 / J. Cell Biol. / Components of a ubiquitin ligase complex specify polyubiquitination and intracellular trafficking of the general amino acid permease by Helliwell (2001)
  26. 10.1093/emboj/19.4.550 / EMBO J. / Degradation of unassembled Vph1p reveals novel aspects of the yeast ER quality control system by Hill (2000)
  27. 10.1016/S0092-8674(00)00080-5 / Cell / Activation of a membrane-bound transcription factor by regulated ubiquitin/proteasome-dependent processing by Hoppe (2000)
  28. 10.1128/MCB.19.2.989 / Mol. Cell. Biol. / 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 by Iraqui (1999)
  29. 10.1016/S0092-8674(00)00077-5 / Cell / RING finger proteins: mediators of ubiquitin ligase activity by Joazeiro (2000)
  30. 10.1007/s002940050201 / Curr. Genet. / STP1, a gene involved in pre-tRNA processing in yeast, is important for amino-acid uptake and transcription of the permease gene BAP2 by Jørgensen (1997)
  31. 10.1002/(SICI)1097-0061(19980130)14:2<103::AID-YEA203>3.0.CO;2-C / Yeast / Mutations in five loci affecting GAP1-independent uptake of neutral amino acids in yeast by Jørgensen (1998)
  32. 10.1016/S0378-1119(99)00535-1 / Gene / The growth of mdp1/rsp5 mutants of Saccharomyces cerevisiae is affected by mutations in the ATP-binding domain of the plasma membrane H+-ATPase by Kaminska (2000)
  33. 10.1016/0092-8674(92)90146-4 / Cell / Ssn6-Tup1 is a general repressor of transcription in yeast by Keleher (1992)
  34. 10.1128/MCB.19.8.5405 / Mol. Cell. Biol. / Ssy1p and Ptr3p are plasma membrane components of a yeast system that senses extracellular amino acids by Klasson (1999)
  35. 10.1016/0005-2736(85)90375-X / Biochim. Biophys. Acta / The detection and classification of membrane-spanning proteins by Klein (1985)
  36. 10.1046/j.1365-2958.1999.01413.x / Mol. Microbiol. / A Saccharomyces cerevisiae G -protein coupled receptor, Gpr1, is specifically required for glucose activation of the cAMP pathway during the transition to growth on glucose by Kraakman (1999)
  37. 10.1091/mbc.12.3.711 / Mol. Biol. Cell / A family of small coiledcoil-forming proteins functioning at the late endosome in yeast by Kranz (2001)
  38. 10.1016/0022-2836(82)90515-0 / J. Mol. Biol. / A simple method of displaying the hydropathic character of a protein by Kyte (1982)
  39. 10.1093/emboj/16.18.5629 / EMBO J. / Grr1 of Saccharomyces cerevisiae is connected to the ubiquitin proteolysis machinery through Skp1: coupling glucose sensing to gene expression and the cell cycle by Li (1997)
  40. 10.1091/mbc.7.12.1953 / Mol. Biol. Cell / A novel signal transduction pathway in Saccharomyces cerevisiae defined by Snf3-regulated expression of HXT6 by Liang (1996)
  41. 10.1093/emboj/17.5.1236 / EMBO J. / The MEP2 ammonium permease regulates pseudohyphal differentiation in Saccharomyces cerevisiae by Lorenz (1998)
  42. 10.1093/genetics/154.2.609 / Genetics / The G protein-coupled receptor GPR1 is a nutrient sensor that regulates pseudohyphal differentiation in Saccharomyces cerevisiae by Lorenz (2000)
  43. 10.1073/pnas.96.20.11364 / Proc. Natl. Acad. Sci. USA / RING fingers mediate ubiquitin-conjugating enzyme (E2)-dependent ubiquitination by Lorick (1999)
  44. 10.1128/JB.182.1.241-243.2000 / J. Bacteriol. / Monoubiquitination is sufficient to signal internalization of the maltose transporter in Saccharomyces cerevisiae by Lucero (2000)
  45. 10.1083/jcb.138.4.731 / J. Cell Biol. / Novel genes involved in endosomal traffic in yeast revealed by suppression of a targeting-defective plasma membrane ATPase mutant by Luo (1997)
  46. 10.1091/mbc.11.2.579 / Mol. Biol. Cell / An endosome-to-plasma membrane pathway involved in trafficking of a mutant plasma membrane ATPase in yeast by Luo (2000)
  47. 10.1128/MCB.17.8.4282 / Mol. Cell. Biol. / A family of ammonium transporters in Saccharomyces cerevisiae by Marini (1997)
  48. 10.1002/j.1460-2075.1991.tb07940.x / EMBO J. / UBA1: an essential yeast gene encoding ubiquitin-activating enzyme by McGrath (1991)
  49. 10.1128/MCB.16.6.2585 / Mol. Cell. Biol. / BRO1, a novel gene that interacts with components of the Pkc1p-mitogen-activated protein kinase pathway in Saccharomyces cerevisiae by Nickas (1996)
  50. 10.1007/s004380000347 / Mol. Gen. Genet. / Transcriptional regulation of the Saccharomyces cerevisiae amino acid permease gene BAP2 by Nielsen (2001)
  51. 10.1016/S0092-8674(00)81707-9 / Cell / Fab1p PtdIns(3)P 5-kinase function essential for protein sorting in the multivesicular body by Odorizzi (1998)
  52. 10.1073/pnas.93.22.12428 / Proc. Natl. Acad. Sci. USA / Two glucose transporters in Saccharomyces cerevisiae are glucose sensors that generate a signal for induction of gene expression by Özcan (1996)
  53. 10.1038/366313a0 / Nature / The yeast DOA4 gene encodes a deubiquitinating enzyme related to a product of the human tre-2 oncogene by Papa (1993)
  54. 10.1002/pro.5560050221 / Protein Sci. / Topology prediction of membrane proteins by Persson (1996)
  55. 10.1091/mbc.3.12.1389 / Mol. Biol. Cell / Morphological classification of the yeast vacuolar protein sorting mutants: evidence for a prevacuolar compartment in class E vps mutants by Raymond (1992)
  56. 10.1083/jcb.137.7.1469 / J. Cell Biol. / Physiological regulation of membrane protein sorting late in the secretory pathway of Saccharomyces cerevisiae by Roberg (1997)
  57. 10.1016/0378-1119(87)90232-0 / Gene / A Saccharomyces cerevisiae genomic plasmid bank based on a centromere-containing shuttle vector by Rose (1987)
  58. 10.1007/s00232001079 / J. Membrane Biol. / Ubiquitination and endocytosis of plasma membrane proteins: role of Nedd4/Rsp5p family of ubiquitin-protein ligases by Rotin (2000)
  59. 10.1002/(SICI)1097-0061(199602)12:2<129::AID-YEA891>3.0.CO;2-O / Yeast / pMPY-ZAP: a reusable polymerase chain reaction-directed gene disruption cassette for Saccharomyces cerevisiae by Schneider (1996)
  60. 10.1093/genetics/122.1.19 / Genetics / A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae by Sikorski (1989)
  61. 10.1091/mbc.9.6.1253 / Mol. Biol. Cell / Nitrogen-regulated ubiquitination of the Gap1 permease of Saccharomyces cerevisiae by Springael (1998)
  62. 10.1006/bbrc.1999.0505 / Biochem. Biophys. Res. Commun. / The yeast Npi1/Rsp5 ubiquitin ligase lacking its N-terminal C2 domain is competent for ubiquitination but not for subsequent endocytosis of the Gap1 permease by Springael (1999)
  63. 10.1242/jcs.112.9.1375 / J. Cell Sci. / NH4+-induced down-regulation of the Saccharomyces cerevisiae Gap1p permease involves its ubiquitination with lysine-63-linked chains by Springael (1999)
  64. 10.1093/genetics/119.2.249 / Genetics / Unlinked non-complementation: isolation of conditional-lethal mutations in each of the tubulin genes of Saccharomyces cerevisiae by Stearns (1988)
  65. 10.1091/mbc.10.8.2583 / Mol. Biol. Cell / The Doa4 deubiquitinating enzyme is required for ubiquitin homeostasis in yeast by Swaminathan (1999)
  66. 10.1016/0092-8674(93)90362-T / Cell / A multisubunit complex associated with the RNA polymerase II CTD and TATA-binding protein in yeast by Thompson (1993)
  67. 10.1016/0378-1119(88)90316-2 / Gene / Cloning and characterization of the CYC8 gene mediating glucose repression in yeast by Trumbly (1988)
  68. 10.1038/35014629 / Nature / Peptides accelerate their uptake by activating a ubiquitin-dependent proteolytic pathway by Turner (2000)
  69. 10.1111/j.1432-1033.1987.tb11170.x / Eur. J. Biochem. / Isolation of the NPR1 gene responsible for the reactivation of ammonia-sensitive amino-acid permeases in Saccharomyces cerevisiae. RNA analysis and gene dosage effects by Vandenbol (1987)
  70. 10.1128/MCB.16.12.6707 / Mol. Cell. Biol. / The Cyc8 (Ssn6)-Tup1 corepressor complex is composed of one Cyc8 and four Tup1 subunits by Varanasi (1996)
  71. {'key': '2022010506122149700_R71', 'first-page': '6500', 'article-title': 'Characterization of TUP1, a mediator of glucose repression in Saccharomyces cerevisiae', 'volume': '10', 'author': 'Williams', 'year': '1990', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / Characterization of TUP1, a mediator of glucose repression in Saccharomyces cerevisiae by Williams (1990)
  72. {'key': '2022010506122149700_R72', 'first-page': '3307', 'article-title': 'The CYC8 and TUP1 proteins involved in glucose repression in Saccharomyces cerevisiae are associated in a protein complex', 'volume': '11', 'author': 'Williams', 'year': '1991', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / The CYC8 and TUP1 proteins involved in glucose repression in Saccharomyces cerevisiae are associated in a protein complex by Williams (1991)
  73. 10.1128/MCB.19.12.8254 / Mol. Cell. Biol. / Ubiquitin metabolism affects cellular response to volatile anesthetics in yeast by Wolfe (1999)
  74. 10.1093/emboj/17.7.1996 / EMBO J. / GPR1 encodes a putative G protein-coupled receptor that associates with the Gpa2p Galpha subunit and functions in a Ras-independent pathway by Xue (1998)
  75. 10.1128/MCB.16.7.3255 / Mol. Cell. Biol. / Bul1, a new protein that binds to the Rsp5 ubiquitin ligase in Saccharomyces cerevisiae by Yashiroda (1996)
  76. 10.1016/S0378-1119(98)00535-6 / Gene / The PY-motif of Bul1 protein is essential for growth of Saccharomyces cerevisiae under various stress conditions by Yashiroda (1998)
Dates
Type When
Created 4 years, 4 months ago (April 28, 2021, 12:04 a.m.)
Deposited 3 years, 7 months ago (Jan. 5, 2022, 1:13 a.m.)
Indexed 3 months, 2 weeks ago (May 7, 2025, 12:43 p.m.)
Issued 24 years, 1 month ago (July 1, 2001)
Published 24 years, 1 month ago (July 1, 2001)
Published Online 24 years, 1 month ago (July 1, 2001)
Published Print 24 years, 1 month ago (July 1, 2001)
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@article{Forsberg_2001, title={Suppressors of ssy1 and ptr3 Null Mutations Define Novel Amino Acid Sensor-Independent Genes in Saccharomyces cerevisiae}, volume={158}, ISSN={1943-2631}, url={http://dx.doi.org/10.1093/genetics/158.3.973}, DOI={10.1093/genetics/158.3.973}, number={3}, journal={Genetics}, publisher={Oxford University Press (OUP)}, author={Forsberg, Hanna and Hammar, Mårten and Andréasson, Claes and Molinér, Annalena and Ljungdahl, Per O}, year={2001}, month=jul, pages={973–988} }