PXD053412

PXD053412 is an original dataset announced via ProteomeXchange.

Title	Loss of Serine/Threonine Protein Phosphatase 6 Severely Impairs Sexual Stage Development in Malaria Parasite Plasmodium berghei
Description	Protein phosphorylation plays a critical role during the development of malaria parasites. Here, we performed a functional analysis of a Plasmodium berghei Ser/Thr protein phosphatase 6 (PbPP6), which was associated with the plasma membrane of macrogametes and ookinetes. Compared with the wild-type P. berghei, genetic disruption/deletion of the pbpp6 gene (∆pbpp6) reduced the asexual growth of the parasites and prolonged the survival of ∆pbpp6-infected mice. The ∆pbpp6 parasites displayed impaired gametogenesis, with a more significant effect on male gametogenesis, which substantially decreased ookinete formation and transmission to mosquitoes. RNA-seq assays revealed that pbpp6 deletion led to over 11-fold down-regulation of the nek3 gene, a regulator of MAPK2 downstream of protein kinase G (PKG)-dependent Ca2+ signaling cascade in male gametogenesis, suggesting that PbPP6 plays a role in the Ca2+ signaling pathway. Meanwhile, we observed altered expression of messenger ribonucleoproteins in the Δpbpp6 parasites, which may affect translational repression of stored mRNAs in female gametocytes and post-fertilization development in mosquitoes. A phospho-proteomic analysis detected increased phosphorylation at the Ser375 site of the phosphoinositide metabolism kinase PIP5K, a target of the PKG. In addition, the Thr699 site of PKG is also a putative target of PbPP6, suggesting that PbPP6 may be involved in a PKG-mediated transcending signaling network to control the sexual development of the malaria parasite. Our study highlighted the significance of protein phosphorylation in sexual development and Plasmodium phosphatases as potential targets for disrupting malaria transmission.
HostingRepository	PRIDE
AnnounceDate	2025-06-27
AnnouncementXML	Submission_2025-06-27_03:32:43.699.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Xiaotong Zhu
SpeciesList	scientific name: Plasmodium berghei ANKA; NCBI TaxID: 5823;
ModificationList	phosphorylated residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-06-26 00:53:47	ID requested
⏵ 1	2025-06-27 03:32:44	announced

Dataset with its publication pending

submitter keyword: Plasmodium

Ser/Thr protein phosphatase 6

gametogenesis

Ca2+ signaling cascade

PKG

Xiaotong Zhu
contact affiliation	Department of Immunology, College of Basic Medical Sciences, China Medical University
contact email	xtzhu@cmu.edu.cn
lab head
Xiaotong Zhu
contact affiliation	Department of Immunology, College of Basic Medical Science, China Medical University
contact email	xtzhu@cmu.edu.cn
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD053412
     1. Label: PRIDE project
     2. Name: Loss of Serine/Threonine Protein Phosphatase 6 Severely Impairs Sexual Stage Development in Malaria Parasite Plasmodium berghei