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Nat Commun. 2017 Jul 5;8(1):63. doi: 10.1038/s41467-017-00053-1.

PfCDPK1 mediated signaling in erythrocytic stages of Plasmodium falciparum.

Author information

1
Eukaryotic Gene Expression laboratory, National Institute of Immunology, New Delhi, 110067, India.
2
Institute of Bioinformatics, Bangalore, Karnataka, 560066, India.
3
Manipal University, Madhav Nagar, Manipal, Karnataka, 576104, India.
4
Harvard TH Chan School of Public Health, Harvard University, Boston, Massachusetts, 02115, USA.
5
Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, 02115, USA.
6
Centre for Bioinformatics, Pondicherry University, Puducherry, 605014, India.
7
Bernhard Nocht Institute for Tropical Medicine and Centre for Structural Systems Biology, Hamburg, 20359, Germany.
8
YU-IOB Center for Systems Biology and Molecular Medicine, Yenepoya University, Mangalore, 575018, India.
9
Proteomics and Bioinformatics Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neuro Sciences, Bangalore, Karnataka, 560029, India.
10
Eukaryotic Gene Expression laboratory, National Institute of Immunology, New Delhi, 110067, India. pushkar@nii.ac.in.

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.Calcium dependent protein kinase 1 (CDPK1) plays an important role in asexual development of Plasmodium falciparum. Using phosphoproteomics and conditional knockdown of CDPK1, the authors here identify CDPK1 substrates and a cross-talk between CDPK1 and PKA, and show the role of CDPK1 in parasite invasion.

PMID:
28680058
PMCID:
PMC5498596
DOI:
10.1038/s41467-017-00053-1
[Indexed for MEDLINE]
Free PMC Article

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