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

J. Biol. Chem., Vol. 281, Issue 30, 21445-21457, July 28, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/30/21445    most recent M512812200v1 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 Protchenko, O. Articles by Philpott, C. C. Search for Related Content PubMed PubMed Citation Articles by Protchenko, O. Articles by Philpott, C. C. Social Bookmarking                      What's this?

A Screen for Genes of Heme Uptake Identifies the FLC Family Required for Import of FAD into the Endoplasmic Reticulum^*

Olga Protchenko¹, Roberto Rodriguez-Suarez, Rachel Androphy, Howard Bussey, and Caroline C. Philpott¹²

From the Liver Diseases Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892 and the Department of Biology, McGill University, Montreal, Quebec H3A 1B1, Canada

Although Candida albicans and Saccharomyces cerevisiae express very similar systems of iron uptake, these species differ in their capacity to use heme as a nutritional iron source. Whereas C. albicans efficiently takes up heme, S. cerevisiae grows poorly on media containing heme as the sole source of iron. We identified a gene from C. albicans that would enhance heme uptake when expressed in S. cerevisiae. Overexpression of CaFLC1 (for flavin carrier 1) stimulated the growth of S. cerevisiae on media containing heme iron. In C. albicans, deletion of both alleles of CaFLC1 resulted in a decrease in heme uptake activity, whereas overexpression of CaFLC1 resulted in an increase in heme uptake. The S. cerevisiae genome contains three genes with homology to CaFLC1, and two of these, termed FLC1 and FLC2, also stimulated growth on heme when overexpressed in S. cerevisiae. The S. cerevisiae Flc proteins were detected in the endoplasmic reticulum and the FLC genes encoded an essential function, as strains deleted for either FLC1 or FLC2 were viable, but deletion of both FLC1 and FLC2 was synthetically lethal. FLC gene deletion resulted in pleiotropic phenotypes related to defects in cell wall integrity. High copy suppressors of this synthetic lethality included three mannosyltransferases, VAN1, KTR4, and HOC1. FLC deletion strains exhibited loss of cell wall mannose phosphates, defects in cell wall assembly, and delayed maturation of carboxypeptidase Y. Permeabilized cells lacking FLC proteins exhibited dramatic loss of FAD import activity. We propose that the FLC genes are required for import of FAD into the lumen of the endoplasmic reticulum, where it is required for disulfide bond formation.

Received for publication, November 30, 2005 , and in revised form, May 3, 2006.

^* 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 Both authors are supported by the Intramural Research Program of the NIDDK, National Institutes of Health.

² To whom correspondence should be addressed: Bldg. 10, Rm. 9B-16, 10 Center Dr., MSC 1800, Bethesda, MD 20892-1800. Tel.: 301-435-4018; Fax: 301-402-0491; E-mail: carolinep{at}intra.niddk.nih.gov.

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]