Plasmodium falciparum histidine triad protein and calmodulin modulates calcium homeostasis and intracellular proteolysis
| Autor: | Fellipe Bronze dos Santos, Taíse Fernanda da Silva Ferrara, Marcos L. Gazarini, Piero Bagnaresi, Alexandre Budu, Mauro F Azevedo, Marcelo Marcondes Ferreira Machado, Adriana K. Carmona, Mayrim M. Gomes Smaul, Sarah El Chamy Maluf, Georgina N. Montagna |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cell signaling Erythrocytes Calmodulin Hydrolases Plasmodium falciparum Biophysics Protozoan Proteins chemistry.chemical_element Calcium Biochemistry 03 medical and health sciences Humans Calcium Signaling Malaria Falciparum Molecular Biology Calcium signaling Calcium metabolism 030102 biochemistry & molecular biology biology Endoplasmic reticulum Cell Biology Cell biology Cytosol 030104 developmental biology chemistry Proteolysis biology.protein Intracellular |
| Zdroj: | Biochemical and biophysical research communications. 503(2) |
| ISSN: | 1090-2104 |
| Popis: | Calcium signaling has an essential role in fundamental processes of Plasmodium life cycle, including migration, cell invasion and parasite development. Two important players in calcium homeostasis, the Histidine Triad (HIT) protein that is implicated in calcium signaling in mammalian cells and calmodulin, which is a classic calcium sensor in eukaryotes are present in Plasmodium falciparum, however theirs function is unknown in the parasite. Here, we investigated the involvement of the P. falciparum Histidine Triad protein (PfHint-1) and calmodulin (PfCaM) in calcium signaling and intracellular proteolysis. For this, we targeted PfHint-1 with a hemagglutinin tail and overexpressed both proteins. We observed that PfHint-1 is expressed throughout the erythrocytic stages and partially colocalizes to the endoplasmic reticulum. Parasites overexpressing PfHint-1 displayed lower ER Ca2+ content and a higher [Ca2+]cyt rise in the parasite cytosol upon Ca2+ addition to the extracellular medium after depletion of ER calcium store. PfCaM-overexpressing parasites exhibit a higher [Ca2+]cyt rise after challenge with the calmodulin inhibitor, calmidazolium. The calcium-dependent proteolytic activity in PfCaM- and PfHint-1-overexpressing parasites was increased and correlated to alterations in calcium homeostasis. Taken together, our results indicate the participation of these proteins in P. falciparum fundamental cellular processes and highlights promising targets for the development of antimalarial drugs. |
| Databáze: | OpenAIRE |
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