The WD40-Protein Pf WLP1 Ensures Stability of the Pf CCp-Based Adhesion Protein Complex in Plasmodium falciparum Gametocytes

Members of the WD40-repeat protein family can be found in all eukaryotic proteomes where they usually serve as interaction platforms for the assembly of large protein complexes and are therefore essential for the integrity of these complexes. In the malaria parasite Plasmodium falciparum , the WD40-repeat protein Pf WLP1 has been shown to interact with members of distinct adhesion protein complexes in the asexual blood stages and gametocyte stages. In this study, we demonstrate that the presence of Pf WLP1 is crucial for both the stability of these gametocyte-specific adhesion complexes as well as for gametocyte maturation and gametogenesis. Using reverse genetics, we generated a Pf WLP1-knockdown parasite line for functional characterization of the protein. Knockdown of Pf WLP1 resulted in a slight reduction of gametocyte numbers and significantly the impaired ability of the gametocytes to exflagellate. Pf WLP1-knockdown further led to reduced protein levels of the Limulus coagulation factor C-like (LCCL)-domain proteins Pf CCp1 and Pf CCp2, which are key components of the adhesion complexes. These findings suggest that the interaction of Pf WLP1 with members of the Pf CCp-based adhesion complex ensures complex stability and thereby contributes to gametocyte viability and exflagellation.