Artikel
Multimeric protein complexes of Plasmodium falciparum gametocytes associate with a WD40 protein and reassemble following parasite transmission to the mosquito
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Veröffentlicht: | 17. Dezember 2014 |
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Gliederung
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During differentiation in the human host, the gametocytes of Plasmodium falciparum display a remarkable number of adhesive proteins on their plasma membrane. These include the PfCCp protein family, six secreted proteins that assemble to multimeric protein complexes (MPCs) within the parasitophorous vacuole. We previously showed that the MPCs are linked to the gametocyte surface via the protein interaction of PfCCp4 with Pfs230, a binding partner of the GPI-anchored Pfs48/45. We now show that lack of Pfs230 in Pfs230-deficient gametocytes results in the destabilization of the parasitophorous vacuolar space. Pfs230 is known to be cleaved at its N-terminal end, once the gametocytes are taken up by blood-feeding mosquitoes and gametogenesis is initiated in the mosquito midgut. Via co-immunoprecipitation assays followed by Western blotting, we demonstrate that Pfs230 processing results in its increased interaction with the MPC, and that impaired Pfs230 processing causes the release of selected PfCCp proteins from the MPC into the medium. We further identified a new MPC interaction partner via co-immunoprecipitation followed by mass spectrometry, the WD40 domain-repeat protein-like protein PfWLP1. WD40 domains are highly conserved among eukaryotes and known to function in MPC assembly by serving as a rigid scaffold for protein interactions. We show that PfWLP1 is expressed both in asexual blood stage parasites and gametocytes. In gametocytes PfWLP1 is primarily associated with the gametocyte surface and here interacts with MPC components. Reverse genetics failed to disrupt the pfwlp1 gene, while hemagglutinin tagging was feasible, suggesting a crucial function for PfWLP1 during blood stage replication. This is the first report on a plasmodial WD40 protein in MPC assembly.
Note: The authors Andreas von Bohl, Andrea Kuehn, and Nina Simon contributed equally.