Calcium signaling in trypanosomatids

• Grant number: 14/13148-9
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: September 01, 2014
• End date: August 31, 2018
• Field of knowledge: Biological Sciences - Biochemistry - Biochemistry of Microorganisms
• Principal Investigator: Roberto Docampo
• Grantee: Miguel Angel Chiurillo Siervo
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 13/50624-0 - Calcium signaling in trypanosomatids, AP.SPEC

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 IP3Rs 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 IP3R-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)

Scientific publications

(8)

(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)

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. (13/50624-0, 14/08995-4, 14/13148-9)

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. (14/08995-4, 14/13148-9, 15/25709-8, 13/50624-0)

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. (14/08995-4, 14/13148-9, 15/25709-8, 13/50624-0)

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. (14/08995-4, 14/13148-9, 15/25709-8, 13/50624-0)

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, p. 8-pg., 2018-06-01. (14/08995-4, 13/50624-0, 15/25709-8, 14/13148-9)

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. (14/08995-4, 14/13148-9, 15/25709-8, 13/50624-0)

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. (14/08995-4, 14/13148-9, 13/50624-0)

LANDER, NOELIA; CHIURILLO, MIGUEL A.; STOREY, MELISSA; VERCESI, ANIBAL E.; DOCAMPO, ROBERTO. CRISPR/Cas9-mediated endogenous C-terminal Tagging of Trypanosoma cruzi Genes Reveals the Acidocalcisome Localization of the Inositol 1,4,5-Trisphosphate Receptor. Journal of Biological Chemistry, v. 291, n. 49, p. 25505-25515, DEC 2 2016. (14/08995-4, 14/13148-9)