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

J. Biol. Chem., Vol. 279, Issue 10, 9222-9232, March 5, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/10/9222    most recent M310502200v1 Alert me when this article is cited 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Santiago, T. C. Articles by Mamoun, C. B. Search for Related Content PubMed PubMed Citation Articles by Santiago, T. C. Articles by Mamoun, C. B. Social Bookmarking                      What's this?

The Plasmodium falciparum PfGatp is an Endoplasmic Reticulum Membrane Protein Important for the Initial Step of Malarial Glycerolipid Synthesis^*

Teresa C. Santiago¶, Rachel Zufferey¶||, Rajendra S. Mehra, Rosalind A. Coleman**, and Choukri Ben Mamoun

From the Center for Microbial Pathogenesis, the Department of Genetics and Developmental Biology, and the ^||Department of Pathology, University of Connecticut Health Center, Farmington, Connecticut 06030-3710, and the ^**Department of Nutrition, University of North Carolina, Chapel Hill, North Carolina 27599

During its 48-h asexual life cycle within human erythrocytes, Plasmodium falciparum grows to many times its own size and divides to produce 16–32 new parasites. This rapid multiplication requires active synthesis of new membranes and is fueled by phospholipid precursors and fatty acids that are scavenged from the human host. Plasmodium membrane biogenesis relies heavily on the expression of parasite enzymes that incorporate these precursors into phospholipids. However, little is known about the genes involved in membrane biogenesis or where this process takes place within the parasite. Here, we describe the analysis in P. falciparum of the first step of phospholipid biosynthesis that controls acylation of glycerol 3-phosphate (GPAT) at the sn-1 position. We show that this activity is of parasite origin and is specific for glycerol 3-phosphate substrate. We have identified the gene, PfGAT, encoding this activity in P. falciparum and reconstituted its codon composition for optimal expression in the yeast Saccharomyces cerevisiae. PfGAT complements the lethality of a yeast double mutant gat1gat2, lacking GPAT activity. Biochemical analysis revealed that PfGatp is a low affinity GPAT enzyme with a high specificity for C16:0 and C16:1 substrates. PfGatp is an integral membrane protein of the endoplasmic reticulum expressed throughout the intraerythrocytic life cycle of the parasite but induced mainly at the trophozoite stage. This study, which describes the first protozoan GPAT gene, reveals an important role for the endoplasmic reticulum in the initial step of Plasmodium membrane biogenesis.

Received for publication, September 23, 2003 , and in revised form, December 9, 2003.

^* This work was supported in part by the University of Connecticut Health Center Fund (to C. B. M.), the Robert Leet and Clara Guthrie Patterson Trust (to C. B. M. and R. Z.), the United States Army Medical Research and Material Command (to C. B. M.), and General Clinical Research Center Grant M01RR06192 from the National Institutes of Health (to the University of Connecticut Health Center, Farmington). 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.

^¶ These authors contributed equally to this work.

Supported by National Institutes of Health Grant DK56598.

To whom correspondence should be addressed: Center for Microbial Pathogenesis, University of Connecticut Health Center, 263 Farmington Ave., MC3710, Farmington, CT 06030-3710. Tel.: 860-679-3544; Fax: 860-679-8130; E-mail: choukri{at}up.uchc.edu.

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

This article has been cited by other articles:

				S. Takebe, W. H. Witola, B. Schimanski, A. Gunzl, and C. Ben Mamoun Purification of Components of the Translation Elongation Factor Complex of Plasmodium falciparum by Tandem Affinity Purification Eukaryot. Cell, April 1, 2007; 6(4): 584 - 591. [Abstract] [Full Text] [PDF]

				W. H. Witola, G. Pessi, K. El Bissati, J. M. Reynolds, and C. B. Mamoun Localization of the Phosphoethanolamine Methyltransferase of the Human Malaria Parasite Plasmodium falciparum to the Golgi Apparatus J. Biol. Chem., July 28, 2006; 281(30): 21305 - 21311. [Abstract] [Full Text] [PDF]

				K. El Bissati, R. Zufferey, W. H. Witola, N. S. Carter, B. Ullman, and C. Ben Mamoun The plasma membrane permease PfNT1 is essential for purine salvage in the human malaria parasite Plasmodium falciparum PNAS, June 13, 2006; 103(24): 9286 - 9291. [Abstract] [Full Text] [PDF]

				R. Zufferey and C. B. Mamoun Leishmania major Expresses a Single Dihydroxyacetone Phosphate Acyltransferase Localized in the Glycosome, Important for Rapid Growth and Survival at High Cell Density and Essential for Virulence J. Biol. Chem., March 24, 2006; 281(12): 7952 - 7959. [Abstract] [Full Text] [PDF]

				G. Pessi, J.-Y. Choi, J. M. Reynolds, D. R. Voelker, and C. B. Mamoun In Vivo Evidence for the Specificity of Plasmodium falciparum Phosphoethanolamine Methyltransferase and Its Coupling to the Kennedy Pathway J. Biol. Chem., April 1, 2005; 280(13): 12461 - 12466. [Abstract] [Full Text] [PDF]

				G. Pessi, G. Kociubinski, and C. B. Mamoun A pathway for phosphatidylcholine biosynthesis in Plasmodium falciparum involving phosphoethanolamine methylation PNAS, April 20, 2004; 101(16): 6206 - 6211. [Abstract] [Full Text] [PDF]