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Vol. 17, Issue 8, 3613-3624, August 2006

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A Cluster of Ring Stage–specific Genes Linked to a Locus Implicated in Cytoadherence in Plasmodium falciparum Codes for PEXEL-negative and PEXEL-positive Proteins Exported into the Host Cell

Tobias Spielmann^*, Paula L. Hawthorne^*, Matthew W.A. Dixon^*, Mandy Hannemann^*, Kathleen Klotz^*, David J. Kemp^*, Nectarios Klonis, Leann Tilley, Katharine R. Trenholme^*, and Donald L. Gardiner^*

*Infectious Diseases and Immunology Division, Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Herston QLD 4029, Australia; and Department of Biochemistry, La Trobe University, Melbourne, VIC 3086, Australia

Submitted April 10, 2006; Revised May 16, 2006; Accepted May 25, 2006
Monitoring Editor: Ralph Isberg

Blood stages of Plasmodium falciparum export proteins into their erythrocyte host, thereby inducing extensive host cell modifications that become apparent after the first half of the asexual development cycle (ring stage). This is responsible for a major part of parasite virulence. Export of many parasite proteins depends on a sequence motif termed Plasmodium export element (PEXEL) or vacuolar transport signal (VTS). This motif has allowed the prediction of the Plasmodium exportome. Using published genome sequence, we redetermined the boundaries of a previously studied region linked to P. falciparum virulence, reducing the number of candidate genes in this region to 13. Among these, we identified a cluster of four ring stage-specific genes, one of which is known to encode an exported protein. We demonstrate that all four genes code for proteins exported into the host cell, although only two genes contain an obvious PEXEL/VTS motif. We propose that the systematic analysis of ring stage-specific genes will reveal a cohort of exported proteins not present in the currently predicted exportome. Moreover, this provides further evidence that host cell remodeling is a major task of this developmental stage. Biochemical and photobleaching studies using these proteins reveal new properties of the parasite-induced membrane compartments in the host cell. This has important implications for the biogenesis and connectivity of these structures.

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

Address correspondence to: Tobias Spielmann ( tobias.spielmann{at}gmail.com) or Donald L. Gardiner ( don.gardiner{at}qimr.edu.au)

Abbreviations used: GAPDH, glyceraldehyde-3-phosphate dehydrogenase; IRBC, infected red blood cell; KAHRP, Knob-associated histidine-rich protein; MAHRP, membrane-associated histidine-rich protein; PEXEL, Plasmodium export element; PfEMP, Plasmodium falciparum erythrocyte membrane protein; PV, parasitophorous vacuole; PVM, parasitophorous vacuole membrane; RBC, red blood cell; REX, ring-exported protein; SBP, skeleton-binding protein; SERP, serine-rich protein; VTS, vacuolar transport signal.

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