Plasmodium falciparum GPCRlike receptor SR25 mediates extracellular K+ sensing coupled to Ca2+ signaling and stress survival

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Moraes, Miriam S. ; Budu, Alexandre ; Singh, Maneesh K. ; Borges-Pereira, Lucas ; Levano-Garcia, Julio ; Curra, Chiara ; Picci, Leonardo ; Pace, Tomasino ; Ponzi, Marta ; Pozzan, Tullio ; Garcia, Celia R. S.

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 7, AUG 25 2017.
• Web of Science Citations: 4

Abstract

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 Ca2+ signaling in the parasites. Changing from high (140 mM) to low (5.4 mM) KCl concentration triggers {[}Ca2+] (cyt) increase in isolated parasites and this Ca2+ rise is blocked either by phospholipase C (PLC) inhibition or by depleting the parasite's internal Ca2+ pools. This response persists even in the absence of free extracellular Ca2+ and cannot be elicited by addition of Na+, Mg2+ or Ca2+. However, when the PfSR25 gene was deleted, no effect on {[}Ca2+] 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. (AU)

• FAPESP's process: 11/51295-5 - Functional genomics in Plasmodium
• Grantee: Célia Regina da Silva Garcia
• Support Opportunities: Research Projects - Thematic Grants