dekoningward-subsetofplasmodium-2002.pdf (401.01 kB)
A subset of Plasmodium falciparum SERA genes are expressed and appear to play an important role in the erythrocytic cycle
journal contribution
posted on 2002-12-06, 00:00 authored by S K Miller, R T Good, D R Drew, M Delorenzi, P R Sanders, A N Hodder, T P Speed, A F Cowman, Tania De Koning-WardTania De Koning-Ward, B S CrabbThe Plasmodium falciparum serine repeat antigen (SERA) has shown considerable promise as a blood stage vaccine for the control of malaria. A related protein, SERPH, has also been described in P. falciparum. Whereas their biological role remains unknown, both proteins possess papain-like protease domains that may provide attractive targets for therapeutic intervention. Genomic sequencing has recently shown that SERA and SERPH are the fifth and sixth genes, respectively, in a cluster of eight SERA homologues present on chromosome 2. In this paper, the expression and functional relevance of these eight genes and of a ninth SERA homologue found on chromosome 9 were examined in blood stage parasites. Using reverse transcriptase-PCR and microarray approaches, we demonstrate that whereas mRNA to all nine SERA genes is synthesized late in the erythrocytic cycle, it is those genes in the central region of the chromosome 2 cluster that are substantially up-regulated at this time. Using antibodies specific to each SERA, it was apparent that SERA4 to -6, and possibly also SERA9, are synthesized in blood stage parasites. The reactivity of antibodies from malaria-immune individuals with the SERA recombinant proteins suggested that SERA2 and SERA3 are also expressed at least in some parasite populations. To examine whether SERA genes are essential to blood stage growth, each of the eight chromosome 2 SERA genes was targeted for disruption. Whereas genes at the periphery of the cluster were mostly dispensable (SERA2 and -3 and SERA7 and -8), those in the central region (SERA4 to -6) could not be disrupted. The inability to disrupt SERA4, -5, and -6 is consistent with their apparent dominant expression and implies an important role for these genes in maintenance of the erythrocytic cycle.
History
Journal
Journal of biological chemistryVolume
277Issue
49Pagination
47524 - 47532Publisher
American Society for Biochemistry and Molecular BiologyLocation
Rockville, Md.Publisher DOI
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ISSN
0021-9258Language
engPublication classification
C1.1 Refereed article in a scholarly journalCopyright notice
2002, The American Society for Biochemistry and Molecular Biology, IncUsage metrics
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AnimalsAntigens, ProtozoanBlotting, SouthernBlotting, WesternChromosomesDNAElectrophoresis, Polyacrylamide GelErythrocytesFemaleFluorescent Antibody Technique, IndirectGlutathione TransferaseMiceMice, Inbred BALB CMicroscopy, FluorescenceModels, GeneticMultigene FamilyOligonucleotide Array Sequence AnalysisPlasmodium falciparumProtein Structure, TertiaryRabbitsRecombinant ProteinsReverse Transcriptase Polymerase Chain ReactionTime FactorsTransfectionScience & TechnologyLife Sciences & BiomedicineBiochemistry & Molecular BiologySERINE-REPEAT ANTIGENBLOOD STAGE ANTIGENPROTECTIVE IMMUNITYMALARIA PARASITESAOTUS MONKEYSPARASITOPHOROUS VACUOLEESCHERICHIA-COLITERMINAL DOMAINANTIBODIESPROTEIN
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