This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Forsberg, H.
Right arrow Articles by Ljungdahl, P. O.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Forsberg, H.
Right arrow Articles by Ljungdahl, P. O.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, February 2001, p. 814-826, Vol. 21, No. 3
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.3.814-826.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Genetic and Biochemical Analysis of the Yeast Plasma Membrane Ssy1p-Ptr3p-Ssy5p Sensor of Extracellular Amino Acids

Hanna Forsberg and Per O. Ljungdahl*

Ludwig Institute for Cancer Research, S-171 77 Stockholm, Sweden

Received 13 September 2000/Returned for modification 17 October 2000/Accepted 13 November 2000

Ssy1p and Ptr3p are known components of a yeast plasma membrane system that functions to sense the presence of amino acids in the extracellular environment. In response to amino acids, this sensing system initiates metabolic signals that ultimately regulate the functional expression of several amino acid-metabolizing enzymes and transport proteins, including multiple, genetically distinct amino acid permeases. We have found that SSY5 encodes a third component of this amino acid sensing system. Mutations in SSY5 manifest phenotypes that are indistinguishable from those resulting from either single ssy1 and ptr3 mutations or ssy5 ssy1 and ssy5 ptr3 double mutations. Although Ssy5p is predicted to be a soluble protein, it exhibits properties indicating that it is a peripherally associated plasma membrane protein. Each of the three sensor components, Ssy1p, Ptr3p, and Ssy5p, adopts conformations and modifications that are dependent upon the availability of amino acids and on the presence of the other two components. These results suggest that these components function as part of a sensor complex localized to the plasma membrane. Consistent with a sensor complex, the overexpression of SSY1 or the unique N-terminal extension of this amino acid permease homologue inactivates the amino acid sensor in a dominant-negative manner. Each of the components of the Ssy1p-Ptr3p-Ssy5p (SPS) signaling system undergoes rapid physical changes, reflected in altered electrophoretic mobility, when leucine is added to cells grown in media lacking amino acids. Furthermore, the levels of each SPS sensor component present in whole-cell extracts diminish upon leucine addition. The rapid physical alterations and reduced levels of sensor components are consistent with their being downregulated in response to amino acid availability. These results reveal the dynamic nature of the amino acid-initiated signals transduced by the SPS sensor.

* Corresponding author. Mailing address: Ludwig Institute for Cancer Research, Box 240, S-171 77 Stockholm, Sweden. Phone: 46 8 728 7108. Fax: 46 8 33 28 12. E-mail: plju{at}licr.ki.se.

Molecular and Cellular Biology, February 2001, p. 814-826, Vol. 21, No. 3
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.3.814-826.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Shin, C.-S., Kim, S. Y., Huh, W.-K. (2009). TORC1 controls degradation of the transcription factor Stp1, a key effector of the SPS amino-acid-sensing pathway in Saccharomyces cerevisiae. J. Cell Sci. 122: 2089-2099 [Abstract] [Full Text]  
  • Hundal, H. S., Taylor, P. M. (2009). Amino acid transceptors: gate keepers of nutrient exchange and regulators of nutrient signaling. Am. J. Physiol. Endocrinol. Metab. 296: E603-E613 [Abstract] [Full Text]  
  • Apostolaki, A., Erpapazoglou, Z., Harispe, L., Billini, M., Kafasla, P., Kizis, D., Penalva, M. A., Scazzocchio, C., Sophianopoulou, V. (2009). AgtA, the Dicarboxylic Amino Acid Transporter of Aspergillus nidulans, Is Concertedly Down-Regulated by Exquisite Sensitivity to Nitrogen Metabolite Repression and Ammonium-Elicited Endocytosis. Eukaryot Cell 8: 339-352 [Abstract] [Full Text]  
  • Liu, Z., Thornton, J., Spirek, M., Butow, R. A. (2008). Activation of the SPS Amino Acid-Sensing Pathway in Saccharomyces cerevisiae Correlates with the Phosphorylation State of a Sensor Component, Ptr3. Mol. Cell. Biol. 28: 551-563 [Abstract] [Full Text]  
  • Cai, H., Hauser, M., Naider, F., Becker, J. M. (2007). Differential Regulation and Substrate Preferences in Two Peptide Transporters of Saccharomyces cerevisiae. Eukaryot Cell 6: 1805-1813 [Abstract] [Full Text]  
  • Boban, M., Ljungdahl, P. O. (2007). Dal81 Enhances Stp1- and Stp2-Dependent Transcription Necessitating Negative Modulation by Inner Nuclear Membrane Protein Asi1 in Saccharomyces cerevisiae. Genetics 176: 2087-2097 [Abstract] [Full Text]  
  • Zargari, A., Boban, M., Heessen, S., Andreasson, C., Thyberg, J., Ljungdahl, P. O. (2007). Inner Nuclear Membrane Proteins Asi1, Asi2, and Asi3 Function in Concert to Maintain the Latent Properties of Transcription Factors Stp1 and Stp2. J. Biol. Chem. 282: 594-605 [Abstract] [Full Text]  
  • Risinger, A. L., Cain, N. E., Chen, E. J., Kaiser, C. A. (2006). Activity-dependent Reversible Inactivation of the General Amino Acid Permease. Mol. Biol. Cell 17: 4411-4419 [Abstract] [Full Text]  
  • Andreasson, C., Heessen, S., Ljungdahl, P. O. (2006). Regulation of transcription factor latency by receptor-activated proteolysis.. Genes Dev. 20: 1563-1568 [Abstract] [Full Text]  
  • Boban, M., Zargari, A., Andreasson, C., Heessen, S., Thyberg, J., Ljungdahl, P. O. (2006). Asi1 is an inner nuclear membrane protein that restricts promoter access of two latent transcription factors. JCB 173: 695-707 [Abstract] [Full Text]  
  • Poulsen, P., Lo Leggio, L., Kielland-Brandt, M. C. (2006). Mapping of an Internal Protease Cleavage Site in the Ssy5p Component of the Amino Acid Sensor of Saccharomyces cerevisiae and Functional Characterization of the Resulting Pro- and Protease Domains by Gain-of-Function Genetics. Eukaryot Cell 5: 601-608 [Abstract] [Full Text]  
  • Cai, H., Kauffman, S., Naider, F., Becker, J. M. (2006). Genomewide Screen Reveals a Wide Regulatory Network for Di/Tripeptide Utilization in Saccharomyces cerevisiae. Genetics 172: 1459-1476 [Abstract] [Full Text]  
  • Eckert-Boulet, N., Larsson, K., Wu, B., Poulsen, P., Regenberg, B., Nielsen, J., Kielland-Brandt, M. C. (2006). Deletion of RTS1, Encoding a Regulatory Subunit of Protein Phosphatase 2A, Results in Constitutive Amino Acid Signaling via Increased Stp1p Processing. Eukaryot Cell 5: 174-179 [Abstract] [Full Text]  
  • Martinez, P., Ljungdahl, P. O. (2005). Divergence of Stp1 and Stp2 Transcription Factors in Candida albicans Places Virulence Factors Required for Proper Nutrient Acquisition under Amino Acid Control. Mol. Cell. Biol. 25: 9435-9446 [Abstract] [Full Text]  
  • Huang, R.-Y., Eddy, M., Vujcic, M., Kowalski, D. (2005). Genome-Wide Screen Identifies Genes Whose Inactivation Confer Resistance to Cisplatin in Saccharomyces cerevisiae. Cancer Res. 65: 5890-5897 [Abstract] [Full Text]  
  • Poulsen, P., Wu, B., Gaber, R. F., Kielland-Brandt, M. C. (2005). Constitutive Signal Transduction by Mutant Ssy5p and Ptr3p Components of the SPS Amino Acid Sensor System in Saccharomyces cerevisiae. Eukaryot Cell 4: 1116-1124 [Abstract] [Full Text]  
  • Abdel-Sater, F., El Bakkoury, M., Urrestarazu, A., Vissers, S., Andre, B. (2004). Amino Acid Signaling in Yeast: Casein Kinase I and the Ssy5 Endoprotease Are Key Determinants of Endoproteolytic Activation of the Membrane-Bound Stp1 Transcription Factor. Mol. Cell. Biol. 24: 9771-9785 [Abstract] [Full Text]  
  • Spielewoy, N., Flick, K., Kalashnikova, T. I., Walker, J. R., Wittenberg, C. (2004). Regulation and Recognition of SCFGrr1 Targets in the Glucose and Amino Acid Signaling Pathways. Mol. Cell. Biol. 24: 8994-9005 [Abstract] [Full Text]  
  • Andreasson, C., Ljungdahl, P. O. (2004). The N-Terminal Regulatory Domain of Stp1p Is Modular and, Fused to an Artificial Transcription Factor, Confers Full Ssy1p-Ptr3p-Ssy5p Sensor Control. Mol. Cell. Biol. 24: 7503-7513 [Abstract] [Full Text]  
  • Abdel-Sater, F., Iraqui, I., Urrestarazu, A., Andre, B. (2004). The External Amino Acid Signaling Pathway Promotes Activation of Stp1 and Uga35/Dal81 Transcription Factors for Induction of the AGP1 Gene in Saccharomyces cerevisiae. Genetics 166: 1727-1739 [Abstract] [Full Text]  
  • Brega, E., Zufferey, R., Mamoun, C. B. (2004). Candida albicans Csy1p Is a Nutrient Sensor Important for Activation of Amino Acid Uptake and Hyphal Morphogenesis. Eukaryot Cell 3: 135-143 [Abstract] [Full Text]  
  • Guaragnella, N., Butow, R. A. (2003). ATO3 Encoding a Putative Outward Ammonium Transporter Is an RTG-independent Retrograde Responsive Gene Regulated by GCN4 and the Ssy1-Ptr3-Ssy5 Amino Acid Sensor System. J. Biol. Chem. 278: 45882-45887 [Abstract] [Full Text]  
  • Gaber, R. F., Ottow, K., Andersen, H. A., Kielland-Brandt, M. C. (2003). Constitutive and Hyperresponsive Signaling by Mutant Forms of Saccharomyces cerevisiae Amino Acid Sensor Ssy1. Eukaryot Cell 2: 922-929 [Abstract] [Full Text]  
  • Kadowaki, M., Kanazawa, T. (2003). Amino Acids as Regulators of Proteolysis. J. Nutr. 133: 2052S-2056 [Abstract] [Full Text]  
  • Andreasson, C., Ljungdahl, P. O. (2002). Receptor-mediated endoproteolytic activation of two transcription factors in yeast. Genes Dev. 16: 3158-3172 [Abstract] [Full Text]  
  • Christie, G. R., Hajduch, E., Hundal, H. S., Proud, C. G., Taylor, P. M. (2002). Intracellular Sensing of Amino Acids in Xenopus laevis Oocytes Stimulates p70 S6 Kinase in a Target of Rapamycin-dependent Manner. J. Biol. Chem. 277: 9952-9957 [Abstract] [Full Text]  
  • Gonzalez-Lopez, C. I., Szabo, R., Blanchin-Roland, S., Gaillardin, C. (2002). Genetic Control of Extracellular Protease Synthesis in the Yeast Yarrowia lipolytica. Genetics 160: 417-427 [Abstract] [Full Text]  
  • Anthony, T. G., Reiter, A. K., Anthony, J. C., Kimball, S. R., Jefferson, L. S. (2001). Deficiency of dietary EAA preferentially inhibits mRNA translation of ribosomal proteins in liver of meal-fed rats. Am. J. Physiol. Endocrinol. Metab. 281: E430-E439 [Abstract] [Full Text]  
  • Forsberg, H., Hammar, M., Andreasson, C., Moliner, A., Ljungdahl, P. O. (2001). Suppressors of ssy1 and ptr3 Null Mutations Define Novel Amino Acid Sensor-Independent Genes in Saccharomyces cerevisiae. Genetics 158: 973-988 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»