Division of Cellular and Applied Infection Biology, Institute of Zoology, RWTH Aachen University, Aachen, Germany.
Front Cell Infect Microbiol. 2022 Jul 18;12:942364. doi: 10.3389/fcimb.2022.942364. eCollection 2022.
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 , the WD40-repeat protein 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 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 WLP1-knockdown parasite line for functional characterization of the protein. Knockdown of WLP1 resulted in a slight reduction of gametocyte numbers and significantly the impaired ability of the gametocytes to exflagellate. WLP1-knockdown further led to reduced protein levels of the coagulation factor C-like (LCCL)-domain proteins CCp1 and CCp2, which are key components of the adhesion complexes. These findings suggest that the interaction of WLP1 with members of the CCp-based adhesion complex ensures complex stability and thereby contributes to gametocyte viability and exflagellation.
WD40 重复蛋白家族的成员存在于所有真核生物的蛋白质组中，它们通常作为组装大型蛋白质复合物的相互作用平台，因此对这些复合物的完整性至关重要。在疟原虫中，WD40 重复蛋白 WLP1 已被证明与无性血期和配子体期不同的黏附蛋白复合物的成员相互作用。在这项研究中，我们证明了 WLP1 的存在对于这些配子体特异性黏附复合物的稳定性以及配子体成熟和配子发生都是至关重要的。我们使用反向遗传学生成了 WLP1 敲低的疟原虫系，以对该蛋白进行功能表征。WLP1 的敲低导致配子体数量略有减少，配子体挥鞭运动的能力显著受损。WLP1 的敲低进一步导致凝血因子 C 样（LCCL）结构域蛋白 CCp1 和 CCp2 的蛋白水平降低，CCp1 和 CCp2 是黏附复合物的关键组成部分。这些发现表明，WLP1 与 CCp 基黏附复合物成员的相互作用确保了复合物的稳定性，从而有助于配子体的存活和挥鞭运动。
