title: Functional analysis of the exported type IV HSP40 protein PfGECO in Plasmodium falciparum gametocytes.
abstract: During Plasmodium falciparum infection, host red blood cell (RBC) remodeling is required for the parasite's survival. Such modifications are mediated by the export of parasite proteins into the RBC that alter the architecture of the RBC membrane and enable cytoadherence. It is probable that some exported proteins also play a protective role against the host defense response. This may be of particular importance for the gametocyte stage of the life cycle that is responsible for malaria transmission, since the gametocyte remains in contact with blood as it proceeds through five morphological stages (I to V) during its 12-day maturation. Using microarray analysis, we identified several genes with encoded secretory or export sequences that were differentially expressed during early gametocytogenesis. One of these, PfGECO, encodes a predicted type IV heat shock protein 40 (HSP40) that we show is expressed in gametocyte stages I to IV and is exported to the RBC cytoplasm. HSPs are traditionally induced under stressful conditions to maintain homeostasis, but PfGECO expression was not increased upon heat shock, suggesting an alternate function. Targeted disruption of PfGECO indicated that the gene is not essential for gametocytogenesis in vitro, and quantitative reverse transcriptase PCR (RT-PCR) showed that there was no compensatory expression of the other type IV HSP40 genes. Although P. falciparum HSP40 members are implicated in the trafficking of proteins to the RBC surface, removal of PfGECO did not affect the targeting of other exported gametocyte proteins. This work has expanded the repertoire of known gametocyte-exported proteins to include a type IV HSP40, PfGECO.
authors.affiliation: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20892, USA. belinda.morahan@nih.gov
authors.forename: Belinda J
authors.initials: BJ
authors.lastname: Morahan
authors.forename: Carolyn
authors.initials: C
authors.lastname: Strobel
authors.forename: Uzma
authors.initials: U
authors.lastname: Hasan
authors.forename: Beata
authors.initials: B
authors.lastname: Czesny
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Mantel
authors.forename: Matthias
authors.initials: M
authors.lastname: Marti
authors.forename: Saliha
authors.initials: S
authors.lastname: Eksi
authors.forename: Kim C
authors.initials: KC
authors.lastname: Williamson
mesh_terms: D004912:Erythrocytes / Q000469:parasitology*; D017125:Genes, Protozoan; D050956:HSP40 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D018869:Heat-Shock Response; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D010963:Plasmodium falciparum / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D015800:Protozoan Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D050956:HSP40 Heat-Shock Proteins; D015800:Protozoan Proteins