PfCDPK1 mediated signaling in erythrocytic stages of Plasmodium falciparum

Sudhir Kumar, Manish Kumar, Roseleen Ekka, Jeffrey D. Dvorin, Aditya S. Paul, Anil K. Madugundu, Tim Gilberger, Harsha Gowda, Manoj T. Duraisingh, T. S. Keshava Prasad and Pushkar Sharma ()
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Sudhir Kumar: National Institute of Immunology
Manish Kumar: Institute of Bioinformatics
Roseleen Ekka: National Institute of Immunology
Jeffrey D. Dvorin: Harvard University
Aditya S. Paul: Harvard University
Anil K. Madugundu: Institute of Bioinformatics
Tim Gilberger: Bernhard Nocht Institute for Tropical Medicine and Centre for Structural Systems Biology
Harsha Gowda: Institute of Bioinformatics
Manoj T. Duraisingh: Harvard University
T. S. Keshava Prasad: Institute of Bioinformatics
Pushkar Sharma: National Institute of Immunology

Nature Communications, 2017, vol. 8, issue 1, 1-13

Abstract: Abstract Calcium Dependent Protein Kinases are key effectors of calcium signaling in malaria parasite. PfCDPK1 is critical for asexual development of Plasmodium falciparum, but its precise function and substrates remain largely unknown. Using a conditional knockdown strategy, we here establish that this kinase is critical for the invasion of host erythrocytes. Furthermore, using a multidisciplinary approach involving comparative phosphoproteomics we gain insights into the underlying molecular mechanisms. We identify substrates of PfCDPK1, which includes proteins of Inner Membrane Complex and glideosome-actomyosin motor assembly. Interestingly, PfCDPK1 phosphorylates PfPKA regulatory subunit (PfPKA-R) and regulates PfPKA activity in the parasite, which may be relevant for the process of invasion. This study delineates the signaling network of PfCDPK1 and sheds light on mechanisms via which it regulates invasion.

Date: 2017
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DOI: 10.1038/s41467-017-00053-1

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