PXD063225-1

PXD063225 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 the Plasmodium berghei Ser/Thr protein phosphatase 6 (PbPP6), which was associated with the plasma membrane of macrogametes and ookinetes. Compared to 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 showed impaired gametogenesis, particularly affecting male gametogenesis, which substantially decreased ookinete formation and transmission to mosquitoes. RNA-seq assays revealed that pbpp6 disruption led to over 11-fold down-regulation of the nek3 gene, a regulator of MAPK2 in the PKG-Ca2+ signaling cascade during male gametogenesis. Several PDEs (α, γ, δ) were also affected, indicating that PbPP6 plays a role in the cGMP-PKG-Ca2+ signaling pathway. Additionally, 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. Consistent with the dysregulated GO terms related to the cGMP-PKG-Ca2+ signaling cascade observed in RNA-seq analysis, the activated gametocytes of ∆pbpp6 exhibited significantly reduced levels of intracellular cGMP, cytosolic Ca2+ mobilization, and DNA replication. Phosphoproteomic analysis detected increased phosphorylation at the Ser508 site of guanylyl cyclase alpha (GCα), suggesting that PbPP6 regulates cGMP-PKG-Ca2+ signaling cascades by modulating the activity of GCα during gametogenesis. This study highlights the potential of targeting PP6 to disrupt malaria transmission.
HostingRepository	PRIDE
AnnounceDate	2025-06-03
AnnouncementXML	Submission_2025-06-02_20:15:14.034.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Xiaotong Zhu
SpeciesList	scientific name: Plasmodium berghei; NCBI TaxID: 5821;
ModificationList	phosphorylated residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2025-04-23 00:24:18	ID requested
⏵ 1	2025-06-02 20:15:14	announced

Dataset with its publication pending

submitter keyword: Loss of Serine/Threonine Protein Phosphatase 6 Severely Impairs Sexual Stage Development in Malaria Parasite Plasmodium berghei

Xiaotong Zhu
contact affiliation	Department of Immunology, College of Basic Medical Science, China Medical University, Shenyang, Liaoning 110122, China
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. PXD063225
     1. Label: PRIDE project
     2. Name: Loss of Serine/Threonine Protein Phosphatase 6 Severely Impairs Sexual Stage Development in Malaria Parasite Plasmodium berghei