Regulation of protein phosphatase type 1 and cell cycle progression by PfLRR1, a novel leucine-rich repeat protein of the human malaria parasite Plasmodium falciparum

Molecular Microbiology
Wassim DaherJamal Khalife

Abstract

The protein called 'suppressor of the dis2 mutant (sds22+)' is an essential regulator of cell division in fission and budding yeasts, where its deletion causes mitotic arrest. Its role in cell cycle control appears to be mediated through the activation of protein phosphatase type 1 (PP1) in Schizosaccharomyces pombe. We have identified the Plasmodium falciparum Sds22 orthologue, which we designated PfLRR1 as it belongs to the leucine-rich repeat protein family. We showed by glutathione-S-transferase pull-down assay that the PfLRR1 gene product interacts with PfPP1, that the PfLRR1-PfPP1 complex is present in parasite extracts and that PfLRR1 inhibits PfPP1 activity. Functional studies in Xenopus oocytes revealed that PfLRR1 interacted with endogenous PP1 and overcame the G2/M cell cycle checkpoint by promoting progression to germinal vesicle breakdown (GVBD). Confirmatory results showing the appearance of GVBD were observed when oocytes were treated with anti-PP1 antibodies or okadaic acid. Taken together, these observations suggest that PfLRR1 can regulate the cell cycle by binding to PP1 and regulating its activity.

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Citations

Apr 28, 2010·The Journal of Biological Chemistry·Wassim DaherJamal Khalife
Jul 16, 2008·Molecular and Biochemical Parasitology·Mikhail A Kutuzov, Alexandra V Andreeva
May 10, 2016·Future Microbiology·Jamal Khalife, Christine Pierrot
May 31, 2017·Molecular Microbiology·Chunlin Yang, Gustavo Arrizabalaga
Nov 16, 2018·Frontiers in Microbiology·Astrid LenneChristine Pierrot
Jul 17, 2020·Nature Communications·Aditya S PaulManoj T Duraisingh
Jun 1, 2019·Scientific Reports·Bénédicte GnangnonChristine Pierrot
Oct 11, 2020·Trends in Parasitology·Jamal KhalifeChristine Pierrot
Apr 2, 2021·Frontiers in Cellular and Infection Microbiology·Chiamaka V UkegbuDina Vlachou
Jul 27, 2021·Parasitology Research·Jenny Nancy Gómez-SandovalM Magdalena Aguirre-García

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