PXD013874

PXD013874 is an original dataset announced via ProteomeXchange.

Title	Essential role of GEXP15, a specific Protein Phosphatase type 1 partner in Plasmodium berghei in asexual erythrocytic proliferation and transmission
Description	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. falciparum and P. berghei. Functional assays showed that GEXP15 was able to increase the PP1 activity and the mutation of the RVxF motif completely abolished this regulation. Immunoprecipitation assays of tagged GEXP15 or PP1 in P. berghei followed by immunoblot or mass spectrometry analyses confirmed their interaction and showed that they are present both in schizont and gametocyte stages in shared protein complexes involved in the spliceosome and proteasome pathways and known to play essential role in parasite development. Phenotypic analysis of viable GEXP15 deficient P. berghei blood parasites showed that they were unable to develop lethal infection in BALB/c mice or to establish experimental cerebral malaria in C57BL/6 mice. Further, although deficient parasites produced gametocytes they did not produce any oocysts/sporozoites indicating a high fitness cost in the mosquito. Global proteomic and phosphoproteomic analyses of GEXP15 deficient schizonts revealed a profound defect with a significant decrease in the abundance and an impact on phosphorylation status of proteins involved in regulation of gene expression or invasion. Moreover, the depletion of GEXP15 seemed to impact mainly the abundance of some specific proteins of female gametocytes. Our study provides the first insight into the contribution of a PP1 regulator to Plasmodium virulence and suggests that GEXP15 affects both the asexual and sexual life cycle.
HostingRepository	PRIDE
AnnounceDate	2019-07-16
AnnouncementXML	Submission_2019-08-01_04:39:00.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD013874
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	SALIOU Jean-Michel
SpeciesList	scientific name: Plasmodium berghei ANKA; NCBI TaxID: 5823;
ModificationList	Propionamide; Oxidation; Acetyl; Carbamidomethyl
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-05-16 04:06:10	ID requested
1	2019-07-16 03:35:51	announced
⏵ 2	2019-08-01 04:39:01	announced	Updated publication reference for PubMed record(s): 31348803.

Hollin T, De Witte C, Fr, é, ville A, Guerrera IC, Chhuon C, Saliou JM, Herbert F, Pierrot C, Khalife J, Essential role of GEXP15, a specific Protein Phosphatase type 1 partner, in Plasmodium berghei in asexual erythrocytic proliferation and transmission. PLoS Pathog, 15(7):e1007973(2019) [pubmed]

submitter keyword: PP1, Plasmodium, phosphatase, IP-MS

Jean-Michel Saliou
contact affiliation	Center for Infection and Immunity of Lille, Inserm U1019-CNRS UMR 8204, Université de Lille, Institut Pasteur de Lille, 1 Rue du Professeur Calmette, F-59000 Lille, France
contact email	jean-michel.saliou@pasteur-lille.fr
lab head
SALIOU Jean-Michel
contact affiliation	Institut Pasteur de Lille
contact email	jean-michel.saliou@pasteur-lille.fr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD013874
     1. Label: PRIDE project
     2. Name: Essential role of GEXP15, a specific Protein Phosphatase type 1 partner in Plasmodium berghei in asexual erythrocytic proliferation and transmission