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Infection and Immunity, October 2004, p. 6095-6105, Vol. 72, No. 10
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.10.6095-6105.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Correct Promoter Control Is Needed for Trafficking of the Ring-Infected Erythrocyte Surface Antigen to the Host Cytosol in Transfected Malaria Parasites

Melanie Rug,1,2 Mark E. Wickham,2 Michael Foley,1 Alan F. Cowman,2 and Leann Tilley1*

Department of Biochemistry, La Trobe University, Melbourne,1 Infection and Immunity, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia2

Received 4 April 2004/ Returned for modification 22 May 2004/ Accepted 15 June 2004

Following invasion of human erythrocytes, the malaria parasite, Plasmodium falciparum, exports proteins beyond the confines of its own plasma membrane to modify the properties of the host red cell membrane. These modifications are critical to the pathogenesis of malaria. Analysis of the P. falciparum genome sequence has identified a large number of molecules with putative atypical signal sequences. The signals remain poorly characterized; however, a number of molecules with these motifs localize to the host erythrocyte. To examine the role of these atypical signal sequences in the export of parasite proteins, we have generated transfected parasites expressing a chimeric protein comprising the N-terminal region of the P. falciparum ring-infected erythrocyte surface antigen (RESA) appended to green fluorescent protein (GFP). This N-terminal region contains a hydrophobic stretch of amino acids that is presumed to act as a noncanonical secretory signal sequence. Modulation of the timing of transgene expression demonstrates that trafficking of malaria proteins into the host erythrocyte is dependant on both the presence of an appropriate transport signal and the timing of expression. Transgene expression under the control of a trophozoite-specific promoter mistargets the chimeric molecule to the parasitophorous vacuole surrounding the parasite. However, expression of RESA-GFP in schizont stages, under the control of the RESA promoter, enables correct trafficking of a population of the chimeric protein to the host erythrocyte.

* Corresponding author. Mailing address: Department of Biochemistry, La Trobe University, Melbourne, 3086 Victoria, Australia. Phone: 61-3-94791375. Fax: 61-3-94792467. E-mail: L.Tilley{at}LaTrobe.edu.au.

Editor: W. A. Petri, Jr.

Infection and Immunity, October 2004, p. 6095-6105, Vol. 72, No. 10
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.10.6095-6105.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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