Proteomics

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Essential role of GEXP15, a specific Protein Phosphatase type 1 partner in Plasmodium berghei in asexual erythrocytic proliferation and transmission


ABSTRACT: In the absence of an effective vaccine and the emerging resistance to artemisinin combination therapy, malaria is still a significant threat to human health. Increasing our understanding of the specific mechanisms of the biology of Plasmodium is essential to propose new strategies to control this infection. Here, we demonstrated that GEXP15, a specific protein in Plasmodium, was able to interact with the PP1 and regulate its phosphatase activity. We showed that both proteins are implicated in common protein complexes involved in the mRNA splicing and proteasome pathways. We reported that the deletion of GEXP15 leads to a loss of parasite virulence during asexual stages and a total abolishment of the capacity of deficient parasites to develop into oocysts. We also found that this deletion affects both protein phosphorylation status and significantly decreases the expression of essential proteins in schizont and gametocyte stages. This study characterizes for the first time a novel molecular pathway through the control of PP1 by an essential and specific Plasmodium regulator, which may contribute to the discovery of new therapeutic targets to control malaria.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Blood Cell

DISEASE(S): Plasmodium Falciparum Malaria

SUBMITTER: Chiara guerrera  

LAB HEAD: GUERRERA Ida Chiara

PROVIDER: PXD013814 | Pride | 2019-07-16

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
20180514_JaKH_2_KO2_P_1_7450.raw Raw
20180514_JaKH_2_KO2_P_2_7451.raw Raw
20180514_JaKH_2_KO2_P_3_7452.raw Raw
20180514_JaKH_2_WT2_P_1_7438.raw Raw
20180514_JaKH_2_WT2_P_2_7439.raw Raw
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Publications

Essential role of GEXP15, a specific Protein Phosphatase type 1 partner, in Plasmodium berghei in asexual erythrocytic proliferation and transmission.

Hollin Thomas T   De Witte Caroline C   Fréville Aline A   Guerrera Ida Chiara IC   Chhuon Cerina C   Saliou Jean-Michel JM   Herbert Fabien F   Pierrot Christine C   Khalife Jamal J  

PLoS pathogens 20190726 7


The essential and distinct functions of Protein Phosphatase type 1 (PP1) catalytic subunit in eukaryotes are exclusively achieved through its interaction with a myriad of regulatory partners. In this work, we report the molecular and functional characterization of Gametocyte EXported Protein 15 (GEXP15), a Plasmodium specific protein, as a regulator of PP1. In vitro interaction studies demonstrated that GEXP15 physically interacts with PP1 through the RVxF binding motif in P. berghei. Functional  ...[more]

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