Role of Calcium Signaling in the Transcriptional Regulation of the Apicoplast Genome ofPlasmodium falciparum

Abstract

Calcium is a universal second messenger that plays an important role in regulatory processes in eukaryotic cells. To understand calcium-dependent signaling in malaria parasites, we analyzed transcriptional responses of Plasmodium falciparum to two calcium ionophores (A23187 and ionomycin) that cause redistribution of intracellular calcium within the cytoplasm. While ionomycin induced a specific transcriptional response defined by up- or downregulation of a narrow set of genes, A23187 caused a developmental arrest in the schizont stage. In addition, we observed a dramatic decrease of mRNA levels of the transcripts encoded by the apicoplast genome during the exposure of P. falciparum to both calcium ionophores. Neither of the ionophores caused any disruptions to the DNA replication or the overall apicoplast morphology. This suggests that the mRNA downregulation reflects direct inhibition of the apicoplast gene transcription. Next, we identify a nuclear encoded protein with a calcium binding domain (EF-hand) that is localized to the apicoplast. Overexpression of this protein (termed PfACBP1) in P. falciparum cells mediates an increased resistance to the ionophores which suggests its role in calcium-dependent signaling within the apicoplast. Our data indicate that the P. falciparum apicoplast requires calcium-dependent signaling that involves a novel protein PfACBP1.

Potential Sabotage of Host Cell Physiology by Apicomplexan Parasites for Their Survival Benefits

“…The translocation of IP3 on to the ER surface causes efflux of Ca 2+ to the cytoplasm by the formation of IP3-Ca 2+ channel ( 20 , 22 ) (Figure 1 ). The increase in the cytoplasmic Ca 2+ levels activates various calcium-dependent proteases and kinases, like calcium-dependent protein kinases (PfCDPK), double C2 domain protein (PfDOC2) which induce the secretion of microneme and rhoptry proteins for cell adherence and invasion ( 20 , 23 , 24 ). The hepatocyte invasion of the sporozoites occurs via Ca 2+ -mediated activation and secretion of microneme proteins, CSP and thrombospondin-related adhesion protein (TRAP) such as Trap-like protein (TLP) ( 12 , 15 , 25 ) (Figure 1 ).…”

Modification of plant cell wall structure accompanied by enhancement of saccharification efficiency using a chemical, lasalocid sodium

“…calcium ions, between membranes. Disturbance of this gradient can trigger cellular responses associated with gene expression alteration 22 23 24 . The difference of effects on the wall sugar composition between LS-treated BY-2 cells and Arabidopsis ( Fig.…”

Plasmodial enzymes in metabolic pathways as therapeutic targets and contemporary strategies to discover new antimalarial drugs: a review

“…In a more recent study, noted that understanding of the function of apicoplasts will benefit in designing better therapeutics through calcium signaling because it plays a vital role in the development and growth of Plasmodium, specifically in apicoplast transcriptional regulation (Cheemadan et al, 2014;M. Rai et al, 2017).…”

“…Rai et al, 2017). Cheemadan et al (2014) studied the role of calcium signaling in the transcriptional regulation of the apicoplast genome of P. falciparum. In order to assess the effect of changing calcium distribution within the cell, the transcriptional responses of P. falciparum to two calcium ionophores was analysed.…”

“…Due to this situation, the authors identified MAL13P1.156, which is a nuclear encoded apicoplast targeted protein that transports a calcium binding domain. Overexpression of the protein causing resistance of P. falciparum towards ionomycin and it was proposed that this protein possibly play an important role in calcium dependent signaling pathways in apicoplast (Cheemadan et al, 2014).…”