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 Zink, S.
Right arrow Articles by Schaffrath, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zink, S.
Right arrow Articles by Schaffrath, R.

 Previous Article  |  Next Article 

Eukaryotic Cell, May 2005, p. 879-889, Vol. 4, No. 5
1535-9778/05/$08.00+0     doi:10.1128/EC.4.5.879-889.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Mannosyl-Diinositolphospho-Ceramide, the Major Yeast Plasma Membrane Sphingolipid, Governs Toxicity of Kluyveromyces lactis Zymocin

Sabrina Zink,1,{dagger} Constance Mehlgarten,1,{dagger} Hiroko K. Kitamoto,2,{dagger} Junko Nagase,2 Daniel Jablonowski,1 Robert C. Dickson,3 Michael J. R. Stark,4 and Raffael Schaffrath1*

Biologicum, Institut für Genetik, Martin-Luther-Universität Halle-Wittenberg, Weinbergweg 10, D-06120 Halle (Saale), Germany,1 National Institute of Agrobiological Sciences, 2-1-2 Kannondai, Tsukuba, Ibaraki 305-8602, Japan,2 Department of Molecular and Cellular Biochemistry, University of Kentucky, College of Medicine, 800 Rose Street, Lexington, Kentucky,3 Division of Gene Regulation and Expression, School of Life Sciences, University of Dundee, MSI/WTB Complex, Dow Street, Dundee DD1 5EH, United Kingdom4

Received 25 January 2005/ Accepted 7 March 2005

Kluyveromyces lactis zymocin, a trimeric ({alpha}ß{gamma}) protein toxin complex, inhibits proliferation of Saccharomyces cerevisiae cells. Here we present an analysis of kti6 mutants, which resist exogenous zymocin but are sensitive to intracellular expression of its inhibitory {gamma}-toxin subunit, suggesting that KTI6 encodes a factor needed for toxin entry into the cell. Consistent with altered cell surface properties, kti6 cells resist hygromycin B, syringomycin E, and nystatin, antibiotics that require intact membrane potentials or provoke membrane disruption. KTI6 is allelic to IPT1, coding for mannosyl-diinositolphospho-ceramide [M(IP)2C] synthase, which produces M(IP)2C, the major plasma membrane sphingolipid. kti6 membranes lack M(IP)2C and sphingolipid mutants that have reduced levels of M(IP)2C precursors, including the sphingolipid building block ceramide survive zymocin. In addition, kti6/ipt1 cells allow zymocin docking but prevent import of its toxic {gamma}-subunit. Genetic analysis indicates that Kti6 is likely to act upstream of lipid raft proton pump Kti10/Pma1, a previously identified zymocin sensitivity factor. In sum, M(IP)2C operates in a plasma membrane step that follows recognition of cell wall chitin by zymocin but precedes the involvement of elongator, the potential toxin target.

* Corresponding author. Mailing address: Biologicum, Institut für Genetik, Martin-Luther-Universität Halle-Wittenberg, Weinbergweg 10, D-06120 Halle (Saale), Germany. Phone: 49-345-5526333. Fax: 49-345-5527151. E-mail: schaffrath{at}genetik.uni-halle.de.

{dagger} These authors contributed equally to the work.

Eukaryotic Cell, May 2005, p. 879-889, Vol. 4, No. 5
1535-9778/05/$08.00+0     doi:10.1128/EC.4.5.879-889.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Paluszynski, J. P., Klassen, R., Meinhardt, F. (2007). Pichia acaciae Killer System: Genetic Analysis of Toxin Immunity. Appl. Environ. Microbiol. 73: 4373-4378 [Abstract] [Full Text]  
  • Gutierrez, A. L., Farage, L., Melo, M. N, Mohana-Borges, R. S, Guerardel, Y., Coddeville, B., Wieruszeski, J.-M., Mendonca-Previato, L., Previato, J. O (2007). Characterization of glycoinositolphosphoryl ceramide structure mutant strains of Cryptococcus neoformans. Glycobiology 17: 1C-1C [Abstract] [Full Text]  
  • Uemura, S., Kihara, A., Iwaki, S., Inokuchi, J.-i., Igarashi, Y. (2007). Regulation of the Transport and Protein Levels of the Inositol Phosphorylceramide Mannosyltransferases Csg1 and Csh1 by the Ca2+-binding Protein Csg2. J. Biol. Chem. 282: 8613-8621 [Abstract] [Full Text]  
  • Zaremberg, V., Gajate, C., Cacharro, L. M., Mollinedo, F., McMaster, C. R. (2005). Cytotoxicity of an Anti-cancer Lysophospholipid through Selective Modification of Lipid Raft Composition. J. Biol. Chem. 280: 38047-38058 [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»