Evidence map›Paper›PMID 40623036›Full record

ArticlePLoS pathogens2025

Loss of serine/threonine protein phosphatase 6 severely impairs sexual stage development in malaria parasite Plasmodium berghei.

Yonghui Feng, Wenyan Gao, Chengqi Wang, Shuangrui Shi, Dan Zhou, Lin Sun, Liying Zhu, Liwang Cui, Yaming Cao, Xiaotong Zhu

Abstract read
In one paragraph

Article in PLoS pathogens, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Yonghui FengDepartment of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, China.
Wenyan GaoDepartment of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, China.
Chengqi WangCenter for Global Health and Infectious Diseases Research, College of Public Health, University of South Florida, Tampa, Florida, United States of America.
Shuangrui ShiDepartment of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, China.
Dan ZhouDepartment of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, China.
Lin SunDepartment of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, China.
Liying ZhuDepartment of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, China.
Liwang CuiDepartment of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, United States of America.
Yaming CaoDepartment of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, China.
Xiaotong ZhuDepartment of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, China.ORCID 0000-0002-9064-586X

Funding

Southeast Asia Malaria Research CenterU19AI089672 · NIAID · UNIVERSITY OF SOUTH FLORIDA · PI CUI, LIWANG · 2010 to 2023
$28.9M
Antigen discovery for transmission-blocking vaccines in Plasmodium vivaxR01AI150533 · NIAID · CHINA MEDICAL UNIVERSITY · PI CAO, YAMING · 2020 to 2024
$677k
NIAID NIH HHS R01 AI150533NIAID NIH HHS U19 AI089672
6 · The paper itself

Abstract

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 is associated with the plasma membrane of macrogametes and ookinetes. Compared to wild-type P. berghei, the genetic disruption of pbpp6 (∆pbpp6) resulted in reduced asexual growth of the parasites and prolonged survival of infected mice. The ∆pbpp6 parasites showed impaired gametogenesis, particularly affecting male gametogenesis, which substantially decreased both ookinete formation and mosquito transmission. Transcriptomic analysis revealed an over 11-fold downregulation of nek3, a regulator of MAPK2 within the PKG-Ca2⁺ signaling cascade, foreshadowing pathway dysregulation that was further evidenced by significantly diminished intracellular cGMP levels, decreased cytosolic Ca2⁺ mobilization, and reduced DNA replication in activated Δpbpp6 gametocytes. Phosphoproteomic analysis detected increased phosphorylation at the Ser508 site of guanylyl cyclase alpha (GCα), indicating that PbPP6 regulates cGMP-PKG-Ca2+ signaling through modulation of GCα activity during gametogenesis. Additionally, we observed altered expression of messenger ribonucleoproteins in the Δpbpp6 parasites, which may affect the translational repression of stored mRNAs in female gametocytes and impact post-fertilization development in mosquitoes. Collectively, this study highlights the potential of targeting PP6 to disrupt malaria transmission.

Indexed as

MalariaPhosphoprotein PhosphatasesPlasmodium bergheiProtozoan ProteinsAnimalsFemaleMaleMicePhosphorylationPhosphoprotein Phosphatasesprotein phosphatase 6Protozoan Proteins

Identifiers

PMID40623036
PMCPMC12233266

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.