A WD40-repeat protein unique to malaria parasites associates with adhesion protein complexes and is crucial for blood stage progeny

Malaria Journal

Research

Marc Spehr¹  Gabriele Pradel²  Andreas von Bohl³  Rainer Fischer⁴  Jude M. Przyborski⁵  Stefan Baumeister⁵  Andrea Kuehn⁶  Vanesa Nkwouano Ngongang⁶  Nina Simon⁶ 

[1] Department of Chemosensation, Institute for Biology II, RWTH Aachen University, 52074, Aachen, Germany;Division of Cellular and Applied Infection Biology, Institute for Biology II, RWTH Aachen University, Worringerweg 1, 52074, Aachen, Germany;Division of Cellular and Applied Infection Biology, Institute for Biology II, RWTH Aachen University, Worringerweg 1, 52074, Aachen, Germany;Institute of Molecular Biotechnology, RWTH Aachen University, Worringerweg 1, 52074, Aachen, Germany;Institute of Molecular Biotechnology, RWTH Aachen University, Worringerweg 1, 52074, Aachen, Germany;Parasitology Section, Faculty of Biology, Philipps University Marburg, Karl-von-Frisch-Straße 8, 35043, Marburg, Germany;Research Center for Infectious Diseases, University of Würzburg, Josef-Schneider-Straße 2/D15, 97080, Würzburg, Germany;

关键词: Malaria;    Plasmodium falciparum;    Merozoite;    Microneme;    Gametocyte;    WD40;    Pf;    Pf;    Pf;   

DOI  :  10.1186/s12936-015-0967-x

 received in 2015-08-22, accepted in 2015-10-27,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundDuring 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.MethodsThe 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.ResultsPfWLP1 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.ConclusionsThis 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.

【 授权许可】

CC BY   
© von Bohl et al. 2015