@article{67398b157f5c43308ec992dcc880ed9e,
title = "The Cryptosporidium signaling kinase CDPK5 plays an important role in male gametogenesis and parasite virulence",
abstract = "The protozoan parasite Cryptosporidium is a leading cause of diarrhea in young children. The parasite's life cycle involves a coordinated and timely progression from asexual to sexual stages, leading to the formation of the transmissible oocyst. Underlying molecular signaling mechanisms orchestrating sexual development are not known. Here, we describe the function of a signaling kinase in Cryptosporidium male gametogenesis. We reveal the expression of Cryptosporidium parvum calcium-dependent protein kinase 5 (CDPK5) during male gamete development and its important role in the egress of mature gametes. Genetic ablation of this kinase results in viable parasites, indicating that this gene is dispensable for parasite survival. Interestingly, cdpk5 deletion decreases parasite virulence and impacts oocyst shedding in immunocompromised mice. Using phosphoproteomics, we identify possible CDPK5 substrates and biological processes regulated by this kinase. Collectively, these findings illuminate parasite cell biology by revealing a mechanism controlling male gamete production and a potential target to block disease transmission.",
keywords = "CP: Microbiology, animal infection, apicomplexan parasite, cell biology, egress, gametogenesis, genetics, kinase, parasite burden, parasitology, phosphoproteomics, virulence",
author = "Nava, {Maria G.} and Joanna Szewczyk and Arrington, {Justine V.} and Tauqeer Alam and Sumiti Vinayak",
note = "We thank Dr. Boris Striepen and Dr. David Sibley for providing the C. parvum antibodies used in immunofluorescence assays. We are grateful to Dr. Moritz Treeck and Dr. Jeffrey Dvorin for providing the BIPPO compound. Figures S1 and 6A and the graphical abstract were created with BioRender.com. We thank the Institute for Genome Biology (IGB) microscopy core, the Proteomics Core Facility of the Roy J. Carver Biotechnology Center, the Department of Comparative Biosciences histology core, and the animal facilities at UIUC for their support. Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), under award number R01AI150961 (to S.V.) and start-up funds from the University of Illinois at Urbana-Champaign. S.V. designed the study. M.G.N. performed most experiments, with contributions from J.S. and S.V. J.S. performed intestinal histology experiments and analyzed histopathological data. J.V.A. conducted proteomics and mass spectrometry data analysis. T.A. performed phylogenetic and sequence analyses. S.V. M.G.N. and T.A. analyzed the data. S.V. wrote the manuscript, with contributions from T.A. M.G.N. and J.V.A. The authors declare no competing interests. We thank Dr. Boris Striepen and Dr. David Sibley for providing the C. parvum antibodies used in immunofluorescence assays. We are grateful to Dr. Moritz Treeck and Dr. Jeffrey Dvorin for providing the BIPPO compound. Figures S1 and 6 A and the graphical abstract were created with BioRender.com . We thank the Institute for Genome Biology (IGB) microscopy core, the Proteomics Core Facility of the Roy J. Carver Biotechnology Center, the Department of Comparative Biosciences histology core, and the animal facilities at UIUC for their support. Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases, National Institutes of Health , under award number R01AI150961 (to S.V.) and start-up funds from the University of Illinois at Urbana-Champaign .",
year = "2024",
month = jun,
day = "25",
doi = "10.1016/j.celrep.2024.114263",
language = "English (US)",
volume = "43",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "6",
}