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PfCDPK1 mediated signaling in erythrocytic stages of Plasmodium falciparum

Author

Listed:
  • Sudhir Kumar

    (National Institute of Immunology)

  • Manish Kumar

    (Institute of Bioinformatics
    Manipal University)

  • Roseleen Ekka

    (National Institute of Immunology)

  • Jeffrey D. Dvorin

    (Harvard University
    Boston Children’s Hospital and Harvard Medical School)

  • Aditya S. Paul

    (Harvard University)

  • Anil K. Madugundu

    (Institute of Bioinformatics
    Pondicherry University)

  • Tim Gilberger

    (Bernhard Nocht Institute for Tropical Medicine and Centre for Structural Systems Biology)

  • Harsha Gowda

    (Institute of Bioinformatics
    Yenepoya University)

  • Manoj T. Duraisingh

    (Harvard University)

  • T. S. Keshava Prasad

    (Institute of Bioinformatics
    Yenepoya University
    National Institute of Mental Health and Neuro Sciences)

  • Pushkar Sharma

    (National Institute of Immunology)

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.

Suggested Citation

  • 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 & Pushkar Sharma, 2017. "PfCDPK1 mediated signaling in erythrocytic stages of Plasmodium falciparum," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00053-1
    DOI: 10.1038/s41467-017-00053-1
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    Cited by:

    1. Kieran Tebben & Salif Yirampo & Drissa Coulibaly & Abdoulaye K. Koné & Matthew B. Laurens & Emily M. Stucke & Ahmadou Dembélé & Youssouf Tolo & Karim Traoré & Amadou Niangaly & Andrea A. Berry & Boure, 2024. "Gene expression analyses reveal differences in children’s response to malaria according to their age," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. Ravish Rashpa & Natacha Klages & Domitille Schvartz & Carla Pasquarello & Mathieu Brochet, 2023. "The Skp1-Cullin1-FBXO1 complex is a pleiotropic regulator required for the formation of gametes and motile forms in Plasmodium berghei," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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