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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Plasmodium falciparum histidine triad protein and calmodulin modulates calcium homeostasis and intracellular proteolysis

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Gomes Smaul, Mayrim Machado [1] ; Budu, Alexandre [2] ; Montagna, Georgina Nuri [1] ; da Silva Ferrara, Taise Fernanda [2] ; Maluf, Sarah El Chamy [2] ; Bagnaresi, Piero [2] ; Ferreira Machado, Marcelo Marcondes [2] ; dos Santos, Fellipe Bronze [2] ; de Azevedo, Mauro Ferreira [3] ; Carmona, Adriana Karaoglanovic [2] ; Gazarini, Marcos Leoni [3]
Total Authors: 11
Affiliation:
[1] Univ Fed Sao Paulo, Dept Microbiol Imunol & Parasitol, Sao Paulo - Brazil
[2] Univ Fed Sao Paulo, Dept Biofis, Sao Paulo - Brazil
[3] Univ Fed Sao Paulo, Dept Biociencias, Santos - Brazil
Total Affiliations: 3
Document type: Journal article
Source: Biochemical and Biophysical Research Communications; v. 503, n. 2, p. 722-728, SEP 5 2018.
Web of Science Citations: 0
Abstract

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. (C) 2018 Elsevier Inc. All rights reserved. (AU)

FAPESP's process: 12/24278-5 - Identification and characterization of cysteine peptidases from Diaphorina citri, Huanglongbing disease vector, and studies of interaction between cysteine peptidases and citrus cystatins
Grantee:Andrea Soares da Costa Fuentes
Support type: Regular Research Grants
FAPESP's process: 16/15298-3 - P. falciparum egress from the host cell: identification of new targets
Grantee:Mauro Ferreira de Azevedo
Support type: Scholarships in Brazil - Young Researchers
FAPESP's process: 14/07138-0 - Plasmodium parasite motility: identification of new candidates for drug targeting and validation of vaccine candidates
Grantee:Georgina Nuri Montagna
Support type: Scholarships in Brazil - Young Researchers
FAPESP's process: 16/02412-2 - Identification and characterization of targets for insect control Diaphorina citri, vector Citrus Disease Huanglongbing
Grantee:Taíse Fernanda da Silva Ferrara
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 15/19316-3 - Regulation of P. falciparum egress from the host cell: identification of new targets
Grantee:Mauro Ferreira de Azevedo
Support type: Research Grants - Young Investigators Grants
FAPESP's process: 13/12913-0 - Calcium-calmodulin of Plasmodium falciparum: identification of ligands and participation in the host-parasite signalling
Grantee:Alexandre Budu
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 15/00689-4 - Study of the internalization of macromolecules in erythrocytes infected with Plasmodium falciparum
Grantee:Sarah El Chamy Maluf
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 15/11861-2 - Involvement of Plasmodium proteases in the pathophysiology of malaria
Grantee:Adriana Karaoglanovic Carmona
Support type: Regular Research Grants
FAPESP's process: 15/07182-2 - Investigation of HINT-1 involvement in calcium cellular signaling in Plasmodium falciparum
Grantee:Mayrim Machado Gomes Smaul
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 11/20941-9 - Development and use of fluorescence techniques for the study of protein conformational changes
Grantee:Marcelo Ferreira Marcondes Machado
Support type: Scholarships in Brazil - Post-Doctorate