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

Abstract

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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-015-0967-x) contains supplementary material, which is available to authorized users.

Genome Wide Identification of Mutational Hotspots in the Apicomplexan Parasite Neospora caninum and the Implications for Virulence

“…The fundamental shared function of all WD40-repeat proteins is facilitating multi-protein complexes, where the repeats serve as a rigid scaffold for protein interactions. The significance of this is that for intracellular protozoan parasites, the efficiency of infection is contingent on the parasite’s capacity for host cell recognition, adhesion, and invasion, which are generally mediated by protein–protein interactions ( von Bohl et al. 2015 ).…”

The s48/45 six-cysteine proteins: mediators of interaction throughout the Plasmodium life cycle

“…Absence of Pfs230 or inhibition of its proteolytic cleavage results in degradation of PfCCp proteins (Simon et al, 2016). A different study also reports the interaction of Pfs230 with PfWL1, a newly identified WD40-repeat protein that might also be part of the PfCCp complex (von Bohl et al, 2015). …”

Spatial and temporal changes in household structure locations using high-resolution satellite imagery for population assessment: an analysis in southern Zambia, 2006-2011

“…Automated feature extraction, including identification of houses, has been successfully utilized in other studies (Tullis et al, 2003; Lo 2007; Lowther et al, 2009; Moss et al, 2011; Wampler et al, 2013; Escamilla et al, 2014; Franke et al, 2015; Kamanga et al, 2015). Regardless of the method used to identify the map feature of interest the spatial statistical approach to understand the changes in imagery between time periods remains applicable.…”

“…Another use for satellite imagery is in the selection of households for targeted interventions. For example, satellite imagery was used in Zambia to enumerate structures and select target areas to receive indoor residual spraying for malaria control (Franke et al, 2015; Kamanga et al, 2015). …”