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| The EMBO Journal
(1999) 18, 5195–5204, doi:10.1093/emboj/18.19.5195 |
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| The A-domain and the thrombospondin-related motif of Plasmodium falciparum TRAP are implicated in the invasion process of mosquito salivary glands |
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| Kai Wengelnik1, Roberta Spaccapelo1, Silvia Naitza1, Kathryn J.H. Robson2, Chris J. Janse3, Francesco Bistoni4, Andrew P. Waters3 and Andrea Crisanti1 |
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1 Imperial College of Science, Technology and Medicine, Department of Biology, Imperial College Road, London SW7 2AZ, UK 2 MRC Molecular Haematology Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK 3 University of Leiden, Department of Parasitology, 2300 RC Leiden, The Netherlands 4 Dipartimento di Medicine Sperimentale, Universita' di Perugia, Italy To whom correspondence should be addressed Andrea Crisanti, acrs@ic.ac.uk Received 8 June 1999; Revised 3 August 1999; Accepted 3 August 1999. |
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| Abstract |
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| Sporozoites from all Plasmodium species analysed so far express the thrombospondin-related adhesive protein (TRAP), which contains two distinct adhesive domains. These domains share sequence and structural homology with von Willebrand factor type A-domain and the type I repeat of human thrombospondin (TSP). Increasing experimental evidence indicates that the adhesive domains bind to vertebrate host ligands and that TRAP is involved, through an as yet unknown mechanism, in the process of sporozoite motility and invasion of both mosquito salivary gland and host hepatocytes. We have generated transgenic P.berghei parasites in which the endogenous TRAP gene has been replaced by either P.falciparum TRAP (PfTRAP) or mutated versions of PfTRAP carrying amino acid substitutions or deletions in the adhesive domains. Plasmodium berghei sporozoites carrying the PfTRAP gene develop normally, are motile, invade mosquito salivary glands and infect the vertebrate host. A substitution in a conserved residue of the A-domain or a deletion in the TSP motif of PfTRAP impairs the sporozoites' ability to invade mosquito salivary glands. Notably, midgut sporozoites from these transgenic parasites are still able to infect mice. Midgut sporozoites carrying a mutation in the A-domain of PfTRAP are motile, while no gliding motility could be detected in sporozoites with a TSP motif deletion. |
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| Keywords: gene complementation, gliding motility, malaria, TRAP |
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