Oral Presentation First Malaria World Congress 2018

PfSR25, a malarial GPCR-like receptor that mediates extracellular K+ sensing coupled to Ca2+ signaling, antimalarial action and stress survival. (#15)

Miriam S Moraes 1 , Maneesh K Singh 1 2 , Alexandre Budu 1 2 , Lucas Borges-Pereira 1 2 , Julio Levano-Garcia 1 , Chiara Curra 1 3 , Tulio Pozzan 4 , Celia Garcia 1 2
  1. Departamento de Fisiologia, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil
  2. Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil
  3. Foundation for Research and Technology-Hellas, Institute of Molecular Biology and Biotechnology, Heraklion, Greece
  4. Department of Biomedical Sciences, University of Padova, Institute of Neuroscience, Unit, National Research Council, Venetian Institute of Molecular Medicine, , Padova, Italy

Plasmodium falciparum, the etiological agent of the human malaria parasite  is exposed to large shifts in K+ concentration during its life cycle. Unraveling the signaling pathways that allow normal parasite growth in diverse ionic environments is fundamental for a better understanding of the disease that affects roughly 500 million people each year. We have demonstrated that the P. falciparum GPCR-like receptor PfSR25 is a monovalent cation sensor and capable of modulating Ca2+ signaling in parasites. Immunofluorescence analysis reveals that PfSR25 is expressed throughout the P. falciparum RBC cycle.

KCl stimulates cytosolic calcium ([Ca2+]cyt) increase in isolated parasites.at Red Blood Cells cycle. The Ca2+ rise is blocked either by PLC inhibition or by depleting the parasite’s internal Ca2+ pools but remains in the absence of free extracellular calcium and cannot be elicited by addition of Na+, Mg2+ or Ca2+. Similar assays performed with PfSR25 knockout parasites (PfSR25-)  had no effect on [Ca2+]cyt in response to change in KCl, thus confirming the relevance of the receptor in the KCl/Ca2+ signaling.

 We have also demonstrated that parasites lacking PfSR25 showed reduced parasitemia when exposed to nitric oxide donor sodium nitroprusside (SNP), antimalarial drug chloroquine and in albumax-deprived condition. In addition, the ability to polymerize the toxic heme into hemozoin is reduced after 2 hours of treatment with the antimalarial piperaquine. To our knowledge this is the first identification of a GPCR-like protein in the human malaria parasite.