Project description:Single cell analysis reveals transcriptional heterogeneity and tightly regulated changes in gene expression during Plasmodium berghei sporozoite development
Project description:Phosphatase type 1 is a major enzyme essential to Plasmodium development. However, the detailed mechanisms underlying its regulation remain to be deciphered. In this work, we report the functional characterization of the Plasmodium berghei LRR1, an ortholog of SDS22, one of the most ancient and conserved Phosphatase type 1 (PP1) interactor. SDS22 has been described as a PP1 regulator essential to critical cellular features such as motility, polarity, epithelium integrity or mitosis completion. Our study shows that in Plasmodium berghei, PbLRR1 is expressed during the intra-erythrocytic developmental cycle and up to the zygote stage during sexual development. PbLRR1 can be found in complex with PbPP1 in both asexual and sexual stages and is able to inhibit the phosphatase activity. Then, genetic analysis demonstrated that PbLRR1 deletion affects the course of the parasite development during early sporogony which manifest by the production of fewer and smaller oocysts. Finally, PbLRR1 interactome analysis associated with phospho-proteomics studies led to the identification of several putative PbLRR1/PbPP1 substrates. Although previously unsuspected PP1 substrates, some of them have been characterized as essential to the parasite sexual development. In addition, and for the first time, we identify the PP1 inhibitor 3 as a substrate of the PP1/LRR1 complex. In summary, this study provides insights into previously unrecognized PbPP1 fine regulation of Plasmodium early sporogony development through its interaction with PbLRR1.
