Abstract
Calcium (Ca2+)-mediated signaling is a conserved mechanism in eukaryotes, including the human malaria parasite, Plasmodium falciparum. Due to its small size (<10 μm) measurement of intracellular Ca2+ in Plasmodium is technically challenging, and thus Ca2+ regulation in this human pathogen is not well understood. Here we analyze Ca2+ homeostasis via a new approach using transgenic P. falciparum expressing the Ca2+ sensor yellow cameleon (YC)-Nano. We found that cytosolic Ca2+ concentration is maintained at low levels only during the intraerythrocytic trophozoite stage (30 nM), and is increased in the other blood stages (>300 nM). We determined that the mammalian SERCA inhibitor thapsigargin and antimalarial dihydroartemisinin did not perturb SERCA activity. The change of the cytosolic Ca2+ level in P. falciparum was additionally detectable by flow cytometry. Thus, we propose that the developed YC-Nano-based system is useful to study Ca2+ signaling in P. falciparum and is applicable for drug screening.
Highlights
As a key second messenger and is maintained at a low level in the cytosol[3]
Because SERCA has been studied as a target of therapeutic intervention in cancer[13], and since P. falciparum genome contains only one SERCA gene[14], targeting this essential pathway related to Ca2+ homeostasis in P. falciparum is an appealing approach to antimalarial drug development
We show that the mammalian SERCA pump inhibitor thapsigargin (TG) and dihydroartemisinin, a current first-line antimalarial, did not change the cytosolic Ca2+ concentration, indicating that these compounds do not inhibit P. falciparum SERCA pump activity
Summary
As a key second messenger and is maintained at a low level in the cytosol[3]. Ca2+ signaling has an essential role in Plasmodium cell differentiation, motility, egress from and invasion into the RBC in the blood stage parasites, as well as predicted roles in other lifecycle stages[4]. We show that the mammalian SERCA pump inhibitor thapsigargin (TG) and dihydroartemisinin (dART), a current first-line antimalarial, did not change the cytosolic Ca2+ concentration, indicating that these compounds do not inhibit P. falciparum SERCA pump activity.
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