title: A member of the CPW-WPC protein family is expressed in and localized to the surface of developing ookinetes.
abstract: BACKGROUND
  Despite the development of malaria control programs, billions of people are still at risk for this infectious disease. Recently, the idea of the transmission-blocking vaccine, which works by interrupting the infection of mosquitoes by parasites, has gained attention as a promising strategy for malaria control and eradication. To date, a limited number of surface proteins have been identified in mosquito-stage parasites and investigated as potential targets for transmission-blocking vaccines. Therefore, for the development of effective transmission-blocking strategies in epidemic areas, it is necessary to identify novel zygote/ookinete surface proteins as candidate antigens.
  
  
  METHODS
  Since the expression of many zygote/ookinete proteins is regulated post-transcriptionally, proteins that are regulated by well-known translational mediators were focused. Through in silico screening, CPW-WPC family proteins were selected as potential zygote/ookinete surface proteins. All experiments were performed in the rodent malaria parasite, Plasmodium yoelii XNL. mRNA and protein expression profiles were examined by RT-PCR and western blotting, respectively, over the course of the life cycle of the malaria parasite. Protein function was also investigated by the generation of gene-disrupted transgenic parasites.
  
  
  RESULTS
  The CPW-WPC protein family, named after the unique WxC repeat domains, is highly conserved among Plasmodium species. It is revealed that CPW-WPC mRNA transcripts are transcribed in gametocytes, while CPW-WPC proteins are expressed in zygote/ookinete-stage parasites. Localization analysis reveals that one of the CPW-WPC family members, designated as PyCPW-WPC-1, is a novel zygote/ookinete stage-specific surface protein. Targeted disruption of the pycpw-wpc-1 gene caused no obvious defects during ookinete and oocyst formation, suggesting that PyCPW-WPC-1 is not essential for mosquito-stage parasite development.
  
  
  CONCLUSIONS
  It is demonstrated that PyCPW-WPC-1 can be classified as a novel, post-transcriptionally regulated zygote/ookinete surface protein. Additional studies are required to determine whether all CPW-WPC family members are also present on the ookinete surface and share similar biological roles during mosquito-stage parasite development. Further investigations of CPW-WPC family proteins may facilitate understanding of parasite biology in the mosquito stage and development of transmission-blocking vaccines.
authors.affiliation: Department of Molecular Parasitology, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Matsuyama, Ehime 791-0295, Japan.
authors.forename: Niwat
authors.initials: N
authors.lastname: Kangwanrangsan
authors.forename: Mayumi
authors.initials: M
authors.lastname: Tachibana
authors.forename: Rachaneeporn
authors.initials: R
authors.lastname: Jenwithisuk
authors.forename: Takafumi
authors.initials: T
authors.lastname: Tsuboi
authors.forename: Suda
authors.initials: S
authors.lastname: Riengrojpitak
authors.forename: Motomi
authors.initials: M
authors.lastname: Torii
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ishino
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000032:analysis* / Q000235:genetics; D015153:Blotting, Western; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D055786:Gene Knockout Techniques; D008565:Membrane Proteins / Q000032:analysis* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010967:Plasmodium yoelii / Q000737:chemistry* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D015053:Zygote / Q000737:chemistry*
chemical_list: D000953:Antigens, Protozoan; D008565:Membrane Proteins