Despite partial success in rolling back malaria, it is still one of the most abundant and deadliest diseases worldwide. The efficient fight against the tropical disease is currently endangered due to the increase in drug resistances. Therefore the identification of novel drug targets is indispensable. The WHO recommends not only to focus on the asexual blood stages, which are causing the main symptoms, but also takes the gametocytes of the intracellular parasite of the genus Plasmodium into account. These are essential for the transmission from the human host to the mosquito vector and are therefore the prime targets for transmission-blocking drugs or vaccines. Thus the aim of this thesis was to functionally characterize two candidate proteins from almost unknown protein classes in P. falciparum.The first candidate belongs to the family of WD40-proteins, which are acting as a scaffold for the assembly of multimeric protein complexes in eukaryotic cells. The findings of this thesis showed that the WD40-protein PfWLP1 (WD40-repeat protein-like protein 1) is one of the few Plasmodium-specific WD40-proteins. It is expressed in the asexual blood and sexual stages and partially co-localizes with structural elements, like microtubules, underneath the plasmamembrane. Furthermore PfWLP1 associates with the adhesion proteins PfAMA1 (apical membrane protein 1) in merozoites and Pfs230 and PfCCp1 (LCCL domain-containing protein 1) in gametocytes. Reverse genetics failed to disrupt the pfwlp1 gene locus, while HA-tagging was feasible, implying a crucial function of PfWLP1 during the intraerythrotic replication. The presented data suggest that PfWLP1 supports the stability of adhesion protein complexes during the life cycle of P. falciparum.The second candidate was PfGPCR1 (G-protein coupled receptor), which was first annotated as a putative GPCR but could be assigned to the family of eukaryotic LanCL-proteins (Lanthionin Synthetase C-like) within this thesis. Further it was shown that PfGPCR1 is exclusively expressed in female gametocytes, belonging to one of the few identified female-specific proteins in P. falciparum. The loss of PfGPCR1 by gene disruption led to a significant reduced transmission of the parasite. Furthermore in vitro protein-protein interaction studies showed that PfGPCR1 interacts with the plasmodial Akt-kinase (PfPKB), comparable to hLanCL2 in human liver cells. The results of this thesis suggest an important role of PfGPCR1 within the PfPKB-signaling pathway in female gametocytes during the transmission of the parasite from the human host to the mosquito vector.The here reported findings display the first characterization of a Plasmodium-specific WD40-potein and of the first plasmodial LanCL-protein and demonstrate the relevance of these protein classes in the life cycle of P. falciparum. Further analyses could not only unravel their unique molecular function in detail, but could also contribute to the development of new antimalarial drugs
