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Studies of the correlation between septin dynamics and Ca2+ homeostasis in muscular cells from Schistosoma mansoni

Grant number: 13/20715-4
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): March 01, 2014
Effective date (End): January 31, 2020
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal Investigator:Ana Paula Ulian de Araujo
Grantee:Ana Eliza Zeraik
Home Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
Associated research grant:14/15546-1 - Septins: comparative studies and the correlation between structure and function, AP.TEM
Associated scholarship(s):16/12505-8 - Characterization of the calcium release-activated (CRAC) channel in the human pathogen Schistosoma mansoni through the study of its components STIM and Orai proteins, BE.EP.PD

Abstract

Septins belong to the GTPase family of proteins and are involved in a variety of cellular functions mainly related to membrane remodeling events. These proteins have been described in several organisms and the number of septins in each organism varies from one (in some species of algae) to 13 (in humans) and frequently form hetero-oligomeric complexes that assemble into filaments. We have recently described four genes encoding septins in Schistosoma mansoni (Zeraik et al. 2013, paper submitted), one of the major causative agents of schistosomiasis. In vivo experiments recently performed in our group with forchlorfenuron (FCF), a drug that affects the dynamics of septin filaments have resulted in a reversible paralysis phenotype in adult worms and cercariae of S. mansoni, indicating that these proteins might be involved in muscle contraction. Recent study (Sharma et al. 2013) revealed that septins are essential components in the activation of a calcium pathway, SOCE (Store-operated calcium entry) and it is known that this ion is essential for muscle contraction. Furthermore, a report have shown that the incubation of S. mansoni adult worms in medium containing a high Mg2+:Ca2+ ratio promoted the inhibition of Ca2+ uptake and a reversible paralysis phenotype (Blair el al. 1992) similar to that observed in our experiments. These observations have lead us to propose the hypothesis in which the change in septin dynamics caused by FCF could affect this calcium channel in S. mansoni, decreasing the Ca2+ entry in the cells as observed in mammalian cells. Therefore, this project focus on the study of FCF effects in S. mansoni, aiming the establishment of correlations between the reversible paralysis caused by this compound and the impairment of the calcium channel dependent on septins. SOCE is an evolutionary conserved pathway and not yet studied in S. mansoni, what makes this calcium channel also pharmacologically attractive, since praziquantel, the main drug against schistosomiasis, affects the calcium homeostase in the cells and promotes paralysis in adult worms, stimulating us to investigate FCF and its derivatives as potential drugs against this disease. The study of this system might provide the establishment of functional relationships among S. mansoni septins and analogous septin complexes of other organisms, contributing to elucidate the function of this family of proteins.

Scientific publications (6)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
TORINI, JULIANA ROBERTA; FERNANDES, ADRIANO DE FREITAS; BALASCO SERRAO, VITOR HUGO; ROMANELLO, LARISSA; BIRD, LOUISE E.; NETTLESHIP, JOANNE E.; OWENS, RAYMOND J.; BRANDAO-NETO, JOSE; ZERAIK, ANA ELIZA; DEMARCO, RICARDO; PEREIRA, HUMBERTO D'MUNIZ. Characterization of a Schistosoma mansoni NDPK expressed in sexual and digestive organs. Molecular and Biochemical Parasitology, v. 231, JUL 2019. Web of Science Citations: 0.
ROMANELLO, LARISSA; ZERAIK, ANA ELIZA; FERNANDES, ADRIANO DE FREITAS; TORINI, JULIANA ROBERTA; BIRD, LOUISE E.; NETTLESHIP, JOANNE E.; RADA, HEATHER; REDDIVARI, YAMINI; OWENS, RAY J.; SERRAO, VITOR HUGO BALASCO; DEMARCO, RICARDO; BRANDAO-NETO, JOSE; PEREIRA, HUMBERTO D'MUNIZ. In vitro and in vivo characterization of the multiple isoforms of Schistosoma mansoni hypoxanthine-guanine phosphoribosyltransferases. Molecular and Biochemical Parasitology, v. 229, p. 24-34, APR 2019. Web of Science Citations: 0.
PINTO, ANDRESSA P. A.; PEREIRA, HUMBERTO M.; ZERAIK, ANA E.; CIOL, HELOISA; FERREIRA, FREDERICO M.; BRANDAO-NETO, JOSE; DEMARCO, RICARDO; NAVARRO, MARCOS V. A. S.; RISI, CRISTINA; GALKIN, VITOLD E.; GARRATT, RICHARD C.; ARAUJO, ANA P. U. Filaments and fingers: Novel structural aspects of the single septin from Chlamydomonas reinhardtii. Journal of Biological Chemistry, v. 292, n. 26, p. 10899-10911, JUN 30 2017. Web of Science Citations: 2.
ZERAIK, ANA ELIZA; BALASCO SERRAO, VITOR HUGO; ROMANELLO, LARISSA; TORINI, JULIANA ROBERTA; CASSAGO, ALEXANDRE; DEMARCO, RICARDO; PEREIRA, HUMBERTO D'MUNIZ. Schistosoma mansoni displays an adenine phosphoribosyltransferase preferentially expressed in mature female gonads and vitelaria. Molecular and Biochemical Parasitology, v. 214, p. 82-86, JUN 2017. Web of Science Citations: 6.
ORCIA, DEBORA; ZERAIK, ANA ELIZA; LOPES, JOSE L. S.; MACEDO, JOCI N. A.; DOS SANTOS, CLARISSA ROMANO; OLIVEIRA, KATIA C.; ANDERSON, LETICIA; WALLACE, B. A.; VERJOVSKI-ALMEIDA, SERGIO; ARAUJO, ANA P. U.; DEMARCO, RICARDO. Interaction of an esophageal MEG protein from schistosomes with a human S100 protein involved in inflammatory response. BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, v. 1861, n. 1, A, p. 3490-3497, JAN 2017. Web of Science Citations: 2.
ZERAIK, ANA ELIZA; STAYKOVA, MARGARITA; FONTES, MARINA GABRIEL; NEMURAITE, INDRE; QUINLAN, ROY; ULIAN ARAUJO, ANA PAULA; DEMARCO, RICARDO. Biophysical dissection of schistosome septins: Insights into oligomerization and membrane binding. Biochimie, v. 131, p. 96-105, DEC 2016. Web of Science Citations: 2.

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