Mapping PP1c and its Inhibitor 2 interactomes reveals conserved and specific networks in asexual and sexual stages of Plasmodium
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ABSTRACT: Malaria parasites require multiple phosphorylation and dephosphorylation steps to drive signaling pathways for proper differentiation and transformation. Several protein phosphatases, including Protein Phosphatase 1 (PP1c), one of the main dephosphorylation enzymes, have been shown to be indispensable for Plasmodium life cycle. PP1c functions are elaborated processes via dynamic interactions with a vast number of binding partners that contribute to its diversity of action. In this study, we have used Plasmodium berghei transgenic parasite strains stably expressing PP1c or its Inhibitor 2 (I2) tagged with mCherry, combined with mCherry affinity pulldown of proteins from asexual and sexual stages and mass spectrometry analyses. Mapped proteins were used to identify interactomes and to cluster functionally related proteins. Our findings confirm previous physical interactions of PP1c and reveal shared and specific biological processes enrichment linked to cellular component assembly in both schizonts and gametocytes, to biosynthetic process/translation in schizonts and to protein transport exclusively in gametocytes. Further, our analysis of PP1c and I2 interactomes reveals that nuclear export mediator factor and peptidyl-prolyl cis-trans isomerase, suggested to be essential in P. falciparum, could be potential targets of the complex PP1c/I2 in both asexual and sexual stages. Our study emphasizes the adaptability of Plasmodium PP1c and provides a fundamental study of the protein interaction landscapes involved in a myriad of events in Plasmodium, suggesting why it is crucial to the parasite and a source for alternative therapeutic strategies.
INSTRUMENT(S): Q Exactive Plus
ORGANISM(S): Plasmodium Berghei Anka Mus Musculus (mouse)
TISSUE(S): Blood
SUBMITTER: Cerina Chhuon
LAB HEAD: Chiara Guerrera
PROVIDER: PXD029283 | Pride | 2022-02-22
REPOSITORIES: Pride
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