Plasmodium falciparum GPCR-like receptor SR25 mediates extracellular K(+) sensing coupled to Ca(2+) signaling and stress survival.

The malaria parasite Plasmodium falciparum is exposed, during its development, to major changes of ionic composition in its surrounding medium. We demonstrate that the P. falciparum serpentine-like receptor PfSR25 is a monovalent cation sensor capable of modulating Ca(2+) signaling in the parasites. Changing from high (140 mM) to low (5.4 mM) KCl concentration triggers [Ca(2+)]cyt increase in isolated parasites and this Ca(2+) rise is blocked either by phospholipase C (PLC) inhibition or by depleting the parasite's internal Ca(2+) pools. This response persists even in the absence of free extracellular Ca(2+) and cannot be elicited by addition of Na(+), Mg(2+) or Ca(2+). However, when the PfSR25 gene was deleted, no effect on [Ca(2+)]cyt was observed in response to changing KCl concentration in the knocked out (PfSR25 (-)) parasite. Finally, we also demonstrate that: i) PfSR25 plays a role in parasite volume regulation, as hyperosmotic stress induces a significant decrease in parasite volume in wild type (wt), but not in PfSR25 (-) parasites; ii) parasites lacking PfSR25 show decreased parasitemia and metacaspase gene expression on exposure to the nitric oxide donor sodium nitroprusside (SNP) and iii), compared to PfSR25 (-) parasites, wt parasites showed a better survival in albumax-deprived condition.