PfCDPK1 mediated signaling in erythrocytic stages of Plasmodium falciparum

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cyclic AMP-Dependent Protein Kinases / genetics
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Erythrocytes / parasitology*
  • Gene Expression Regulation / physiology*
  • Gene Expression Regulation, Enzymologic
  • Organisms, Genetically Modified
  • Plasmodium falciparum / physiology*
  • Protein Kinase Inhibitors / metabolism
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • Protein Subunits
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism*


  • Protein Kinase Inhibitors
  • Protein Subunits
  • Protozoan Proteins
  • Protein Kinases
  • calcium-dependent protein kinase-1, Plasmodium falciparum
  • Cyclic AMP-Dependent Protein Kinases