HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 10, 6376-6384, March 10, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/10/6376    most recent M512115200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Panwar, S. L. Articles by Moye-Rowley, W. S. Search for Related Content PubMed PubMed Citation Articles by Panwar, S. L. Articles by Moye-Rowley, W. S. Social Bookmarking                      What's this?

Long Chain Base Tolerance in Saccharomyces cerevisiae Is Induced by Retrograde Signals from the Mitochondria^*

From the Department of Physiology and Biophysics, University of Iowa, Iowa City, Iowa 52242

Saccharomyces cerevisiae cells lacking their mitochondrial DNA (⁰ cells) respond to this loss of genetic information by induction of a program of nuclear gene expression called the retrograde response. Expression of genes involved in multidrug resistance and sphingolipid biosynthesis is coordinately induced in ⁰ cells by the zinc cluster transcription factor Pdr3p. In this report, we identify a membrane protein involved in control of intracellular levels of a sphingolipid precursor as a transcriptional target of the Pdr3p-mediated retrograde response. These sphingolipid precursors are called long chain bases (LCBs) and increased LCB levels are growth inhibitory. This membrane protein has been designated Rsb1p and has previously been shown to act as a LCB transporter protein and to be a component of the endoplasmic reticulum. These earlier studies used an amino-terminal truncated form of Rsb1p. Here we employ a full-length form of Rsb1p and find that this protein is localized to the plasma membrane and is modified by N-linked glycosylation. Two glycosylation sites are present in the Rsb1p and both are required for normal LCB resistance. Mutational analysis of the RSB1 promoter revealed that two Pdr3p binding sites are present and both of these are required for normal retrograde induction of transcription. LCB tolerance is strongly increased in ⁰ cells but this increase is ablated in ⁰ rsb1 cells. Together, these data indicate Pdr3p activation of RSB1 transcription is an important feature of the retrograde response allowing normal detoxification of an endogenous sphingolipid precursor.

Received for publication, November 10, 2005 , and in revised form, December 22, 2005.

^* This work was supported by National Institutes of Health GM49825. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: 6-530 Bowen Science Bldg., University of Iowa, IA City, IA 52242. Tel.: 319-335-7874; Fax: 319-335-7330; E-mail: scott-moye-rowley{at}uiowa.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				O. Protchenko, M. Shakoury-Elizeh, P. Keane, J. Storey, R. Androphy, and C. C. Philpott Role of PUG1 in Inducible Porphyrin and Heme Transport in Saccharomyces cerevisiae Eukaryot. Cell, May 1, 2008; 7(5): 859 - 871. [Abstract] [Full Text] [PDF]

				M. Ikeda, A. Kihara, A. Denpoh, and Y. Igarashi The Rim101 Pathway Is Involved in Rsb1 Expression Induced by Altered Lipid Asymmetry Mol. Biol. Cell, May 1, 2008; 19(5): 1922 - 1931. [Abstract] [Full Text] [PDF]

				C. Schuller, Y. M. Mamnun, H. Wolfger, N. Rockwell, J. Thorner, and K. Kuchler Membrane-active Compounds Activate the Transcription Factors Pdr1 and Pdr3 Connecting Pleiotropic Drug Resistance and Membrane Lipid Homeostasis in Saccharomyces cerevisiae Mol. Biol. Cell, December 1, 2007; 18(12): 4932 - 4944. [Abstract] [Full Text] [PDF]

				K. Gulshan and W. S. Moye-Rowley Multidrug Resistance in Fungi Eukaryot. Cell, November 1, 2007; 6(11): 1933 - 1942. [Full Text] [PDF]