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Calcium signaling in trypanosomatids

Grant number: 13/50624-0
Support type:Research Projects - SPEC Program
Duration: March 01, 2014 - February 29, 2020
Field of knowledge:Biological Sciences - Biochemistry
Principal Investigator:Roberto Docampo
Grantee:Roberto Docampo
Visiting researcher institution: University of Georgia (UGA), United States
Home Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Co-Principal Investigators:Silvia N. J. Moreno
Associated scholarship(s):17/25084-3 - Pyruvate metabolism function identification in Trypanosoma cruzi, BP.PD
14/13148-9 - Calcium signaling in trypanosomatids, BP.PD
14/08995-4 - Calcium signaling in trypanosomatids, BP.PD

Abstract

Regulation of Ca2+ homeostasis in trypanosomes differs significantly from that in mammalian cells. Trypanosomes possess an abundant acidic calcium store, the acidocalcisome, which is also rich in polyphosphate. Recent results from our group have indicated that acidocalcisomes possess an inositol 1,4,5-trisphosphate receptor (IP3R). These channels are usually located in the endoplasmic reticulum (ER) of mammalian cells. The IP3R is the primary cytosolic target responsible for the initiation of intracellular Ca2+ signaling in most eukaryotic cells. The release of Ca2+ via lP3Rs stimulates activities critical for life, but under some conditions IP3R-mediated Ca2+ signals are subverted to cause cell death, suggesting that this pathway is of potential therapeutic significance. The Ca2+ flow is facilitated by the close lP3R-mitochondrial calcium uniporter (MCU) connection. We hypothesize that Ca2+ signaling through the trypanosome IP3R has roles in growth in vitro and in vivo, and that the mitochondria of trypanosomes exert a regulatory role in Ca2+ signaling. The characterization of the pathways involving Ca2+ signaling in trypanosomes will lead to important insights into the biology of these parasites, the evolution of eukaryotic cells, and ultimately novel targets for anti-parasitic intervention. Our long-term goal is to uncover the Ca2+ signaling pathways in trypanosomes and with this information influence the design of therapeutic agents for parasite control. (AU)

Articles published in Agência FAPESP Newsletter about the research grant
Novel method is used to edit genome of parasite that causes Chagas disease 

Scientific publications (12)
(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)
CHIURILLO, MIGUEL A.; LANDER, NOELIA; BERTOLINI, MAYARA S.; VERCESI, ANIBAL E.; DOCAMPO, ROBERTO. Functional analysis and importance for host cell infection of the Ca2+-conducting subunits of the mitochondrial calcium uniporter of Trypanosoma cruzi. MOLECULAR BIOLOGY OF THE CELL, v. 30, n. 14, p. 1676-1690, JUL 1 2019. Web of Science Citations: 1.
BERTOLINI, MAYARA S.; CHIURILLO, MIGUEL A.; LANDER, NOELIA; VERCESI, ANIBAL E.; DOCAMPO, ROBERTO. MICU1 and MICU2 Play an Essential Role in Mitochondrial Ca2+ Uptake, Growth, and Infectivity of the Human Pathogen Trypanosoma cruzi. MBIO, v. 10, n. 3 MAY-JUN 2019. Web of Science Citations: 1.
LANDER, NOELIA; CHIURILLO, MIGUEL A.; BERTOLINI, MAYARA S.; STOREY, MELISSA; VERCESI, ANIBAL E.; DOCAMPO, ROBERTO. Calcium-sensitive pyruvate dehydrogenase phosphatase is required for energy metabolism, growth, differentiation, and infectivity of Trypanosoma cruzi. Journal of Biological Chemistry, v. 293, n. 45, p. 17402-17417, NOV 9 2018. Web of Science Citations: 4.
LANDER, NOELIA; CHIURILLO, MIGUEL A.; BERTOLINI, MAYARA S.; DOCAMPO, ROBERTO; VERCESI, ANIBAL E. The mitochondrial calcium uniporter complex in trypanosomes. Cell Biology International, v. 42, n. 6, SI, p. 656-663, JUN 2018. Web of Science Citations: 2.
LANDER, NOELIA; CHIURILLO, MIGUEL A.; VERCESI, ANIBAL E.; DOCAMPO, ROBERTO. Endogenous C-terminal Tagging by CRISPR/Cas9 in Trypanosoma cruzi. BIO-PROTOCOL, v. 7, n. 10 MAY 20 2017. Web of Science Citations: 7.
CHIURILLO, MIGUEL A.; LANDER, NOELIA; BERTOLINI, MAYARA S.; STOREY, MELISSA; VERCESI, ANIBAL E.; DOCAMPO, ROBERTO. Different Roles of Mitochondrial Calcium Uniporter Complex Subunits in Growth and Infectivity of Trypanosoma cruzi. MBIO, v. 8, n. 3 MAY-JUN 2017. Web of Science Citations: 23.
DOCAMPO, ROBERTO. The origin and evolution of the acidocalcisome and its interactions with other organelles. Molecular and Biochemical Parasitology, v. 209, n. 1-2, SI, p. 3-9, SEP-OCT 2016. Web of Science Citations: 8.
LANDER, NOELIA; CHIURILLO, MIGUEL A.; DOCAMPO, ROBERTO. Genome Editing by CRISPR/Cas9: A Game Change in the Genetic Manipulation of Protists. Journal of Eukaryotic Microbiology, v. 63, n. 5, p. 679-690, SEP-OCT 2016. Web of Science Citations: 26.
LANDER, NOELIA; CORDEIRO, CIRO; HUANG, GUOZHONG; DOCAMPO, ROBERTO. Polyphosphate and acidocalcisomes. BIOCHEMICAL SOCIETY TRANSACTIONS, v. 44, n. 1, p. 1-6, FEB 15 2016. Web of Science Citations: 20.
LANDER, NOELIA; LI, ZHU-HONG; NIYOGI, SAYANTANEE; DOCAMPO, ROBERTO. CRISPR/Cas9-Induced Disruption of Paraflagellar Rod Protein 1 and 2 Genes in Trypanosoma cruzi Rteveals Their Role in Flagellar Attachment. MBIO, v. 6, n. 4 JUL-AUG 2015. Web of Science Citations: 57.
DOCAMPO, ROBERTO; HUANG, GUOZHONG. Calcium signaling in trypanosomatid parasites. Cell Calcium, v. 57, n. 3, SI, p. 194-202, MAR 2015. Web of Science Citations: 22.
DOCAMPO, ROBERTO; VERCESI, ANIBAL E.; HUANG, GUOZHONG. Mitochondrial calcium transport in trypanosomes. Molecular and Biochemical Parasitology, v. 196, n. 2, p. 108-116, SEP 2014. Web of Science Citations: 15.

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