title: A WD40-repeat protein unique to malaria parasites associates with adhesion protein complexes and is crucial for blood stage progeny.
abstract: BACKGROUND
  During development in human erythrocytes, Plasmodium falciparum parasites display a remarkable number of adhesive proteins on their plasma membrane. In the invasive merozoites, these include members of the PfMSP1 and PfAMA1/RON complexes, which facilitate contact between merozoites and red blood cells. In gametocytes, sexual precursor cells mediating parasite transmission to the mosquito vector, plasma membrane-associated proteins primarily belong to the PfCCp and 6-cys families with roles in fertilization. This study describes a newly identified WD40-repeat protein unique to Plasmodium species that associates with adhesion protein complexes of both merozoites and gametocytes.
  
  
  METHODS
  The WD40-repeat protein-like protein PfWLP1 was identified via co-immunoprecipitation assays followed by mass spectrometry and characterized using biochemical and immunohistochemistry methods. Reverse genetics were employed for functional analysis.
  
  
  RESULTS
  PfWLP1 is expressed both in schizonts and gametocytes. In mature schizonts, the protein localizes underneath the merozoite micronemes and interacts with PfAMA1, while in gametocytes PfWLP1 primarily accumulates underneath the plasma membrane and associates with PfCCp1 and Pfs230. Reverse genetics failed to disrupt the pfwlp1 gene, while haemagglutinin-tagging was feasible, suggesting a crucial function for PfWLP1 during blood stage replication.
  
  
  CONCLUSIONS
  This is the first report on a plasmodial WD40-repeat protein associating with cell adhesion proteins. Since WD40 domains are known to mediate protein-protein contact by serving as a rigid scaffold for protein interactions, the presented data suggest that PfWLP1 supports the stability of adhesion protein complexes of the plasmodial blood stages.
authors.affiliation: Division of Cellular and Applied Infection Biology, Institute for Biology II, RWTH Aachen University, Worringerweg 1, 52074, Aachen, Germany. andreas.von.bohl@rwth-aachen.de.|Institute of Molecular Biotechnology, RWTH Aachen University, Worringerweg 1, 52074, Aachen, Germany. andreas.von.bohl@rwth-aachen.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: von Bohl
authors.affiliation: Research Center for Infectious Diseases, University of Würzburg, Josef-Schneider-Straße 2/D15, 97080, Würzburg, Germany. andrea.kuhn@isglobal.org.
authors.forename: Andrea
authors.initials: A
authors.lastname: Kuehn
authors.affiliation: Research Center for Infectious Diseases, University of Würzburg, Josef-Schneider-Straße 2/D15, 97080, Würzburg, Germany. nina.simon@mbt.uni-erlangen.de.
authors.forename: Nina
authors.initials: N
authors.lastname: Simon
authors.affiliation: Research Center for Infectious Diseases, University of Würzburg, Josef-Schneider-Straße 2/D15, 97080, Würzburg, Germany. vanesa.nkwouano@gmail.com.
authors.forename: Vanesa Nkwouano
authors.initials: VN
authors.lastname: Ngongang
authors.affiliation: Department of Chemosensation, Institute for Biology II, RWTH Aachen University, 52074, Aachen, Germany. m.spehr@sensorik.rwth-aachen.de.
authors.forename: Marc
authors.initials: M
authors.lastname: Spehr
authors.affiliation: Parasitology Section, Faculty of Biology, Philipps University Marburg, Karl-von-Frisch-Straße 8, 35043, Marburg, Germany. baumeist@staff.uni-marburg.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Baumeister
authors.affiliation: Parasitology Section, Faculty of Biology, Philipps University Marburg, Karl-von-Frisch-Straße 8, 35043, Marburg, Germany. przybors@staff.uni-marburg.de.
authors.forename: Jude M
authors.initials: JM
authors.lastname: Przyborski
authors.affiliation: Institute of Molecular Biotechnology, RWTH Aachen University, Worringerweg 1, 52074, Aachen, Germany. rainer.fischer@ime.fraunhofer.de.
authors.forename: Rainer
authors.initials: R
authors.lastname: Fischer
authors.affiliation: Division of Cellular and Applied Infection Biology, Institute for Biology II, RWTH Aachen University, Worringerweg 1, 52074, Aachen, Germany. pradel@bio2.rwth-aachen.de.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Pradel
mesh_terms: D000818:Animals; D001671:Biochemistry; D002448:Cell Adhesion; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D013058:Mass Spectrometry; D010963:Plasmodium falciparum / Q000737:chemistry* / Q000502:physiology*; D015800:Protozoan Proteins / Q000302:isolation & purification* / Q000378:metabolism*; D059386:Reverse Genetics
chemical_list: D015800:Protozoan Proteins