Presence of a thapsigargin-sensitive calcium pump in Trypanosoma evansi: Immunological, physiological, molecular and structural evidences

Pérez-Gordones, María Carolina; Serrano, María Luisa; Rojas, Héctor; Martı́nez, Juan Carlos; Uzcanga, Graciela L.; Mendoza, M.

doi:10.1016/j.exppara.2015.08.017

Cited by 9 publications

(7 citation statements)

References 56 publications

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“…Calmodulin and SERCA) or derived early in the evolution of the eukaryotes (e.g. IP3R) (Nolan et al, 1994;Moreno and Docampo, 2003;Reiner et al, 2003;Prole and Taylor, 2011;Plattner and Verkhratsky, 2013;Verkhratsky and Parpura, 2014;Perez-Gordones et al, 2015). Other proteins show a patchier distribution in lineages outside of metazoans (e.g.…”

Section: Introductionmentioning

confidence: 99%

Functional Innovation in the Evolution of the Calcium-Dependent System of the Eukaryotic Endoplasmic Reticulum

et al. 2020

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The origin of eukaryotes was marked by the emergence of several novel subcellular systems. One such is the calcium (Ca 2+)-stores system of the endoplasmic reticulum, which profoundly influences diverse aspects of cellular function including signal transduction, motility, division, and biomineralization. We use comparative genomics and sensitive sequence and structure analyses to investigate the evolution of this system. Our findings reconstruct the core form of the Ca 2+-stores system in the last eukaryotic common ancestor as having at least 15 proteins that constituted a basic system for facilitating both Ca 2+ flux across endomembranes and Ca 2+-dependent signaling. We present evidence that the key EF-hand Ca 2+-binding components had their origins in a likely bacterial symbiont other than the mitochondrial progenitor, whereas the protein phosphatase subunit of the ancestral calcineurin complex was likely inherited from the asgard archaeal progenitor of the stem eukaryote. This further points to the potential origin of the eukaryotes in a Ca 2+-rich biomineralized environment such as stromatolites. We further show that throughout eukaryotic evolution there were several acquisitions from bacteria of key components of the Ca 2+-stores system, even though no prokaryotic lineage possesses a comparable system. Further, using quantitative measures derived from comparative genomics we show that there were several rounds of lineage-specific gene expansions, innovations of novel gene families, and gene losses correlated with biological innovation such as the biomineralized molluscan shells, coccolithophores, and animal motility. The burst of innovation of new genes in animals included the wolframin protein associated with Wolfram syndrome in humans. We show for the first time that it contains previously unidentified Sel1, EF-hand, and OB-fold domains, which might have key roles in its biochemistry.

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Section: Introductionmentioning

confidence: 99%

Functional Innovation in the Evolution of the Calcium-Dependent System of the Eukaryotic Endoplasmic Reticulum

et al. 2020

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“…(A) Molecular structure of BODIPY–thapsigargin derivative 6 with a fluorophore attached at the C-8 (red dot) position. Fluorescent images of T. evansi parasite stained with H-300 anti-SERCA antibody (B- i ), BODIPY-FL thapsigargin 6 (B- i i ), and merged (B- iii ) . Copyright 2015, Elsevier Ltd.…”

Section: Sesquiterpenesmentioning

confidence: 99%

“…The binding site of thapsigargin at SERCA was described by Skytte et al, and the mechanism of inhibition in eukaryotic organisms was studied previously . The fluorescent commercial probe thapsigargin–BODIPY derivative 6 (Figure A) has widely contributed to SERCA research. − Recently, Pérez-Gordones et al used conjugate 6 to localize a SERCA-like calcium pump in Trypanosoma evansi (Figure B). These results showed that thapsigargin or thapsigargin derivatives could be used as anti- T. evansi drugs.…”

Section: Sesquiterpenesmentioning

confidence: 99%

Terpenes and Terpenoids Conjugated with BODIPYs: An Overview of Biological and Chemical Properties

Stanková,

Jurášek,

Hajdúch

et al. 2024

J. Nat. Prod.

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Advancements in small-molecule research have created the need for sensitive techniques to accurately study biological processes in living systems. Fluorescent-labeled probes have become indispensable tools, particularly those that use boron−dipyrromethene (BODIPY) dyes. Terpenes and terpenoids are organic compounds found in nature that offer diverse biological activities, and BODIPY-based probes play a crucial role in studying these compounds. Monoterpene−BODIPY conjugates have exhibited potential for staining bacterial and fungal cells. Sesquiterpene−BODIPY derivatives have been used to study sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA), indicating their potential for drug development. Owing to their unique properties, diterpenes have been investigated using BODIPY conjugates to evaluate their mechanisms of action. Triterpene−BODIPY conjugates have been synthesized for biological studies, with different spacers affecting their cytotoxicity. Fluorescent probes, inspired by terpenoid-containing vitamins, have also been developed. Derivatives of tocopherol, coenzyme Q10, and vitamin K1 can provide insights into their oxidation−reduction abilities. All these probes have diverse applications, including the study of cell membranes to investigate immune responses and antioxidant properties. Further research in this field can help better understand and use terpenes and terpenoids in various biological contexts.

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“…The uptake of Ca +2 in mammalian cells is mediated by the sarco/endoplasmic reticulum Ca 2+ calcium ATPase (SERCA). Orthologs for the SERCA-type Ca 2+ ATPase protein has been identified and characterized in T. brucei ( Nolan et al., 1994 ), T. evansi ( Mendoza et al., 2004 ; Pérez-Gordones et al, 2015 ), T. cruzi ( Furuya et al, 2001 ) and Leishmania spp ( Lu et al., 1997 ; Rodriguez et al, 2002 , for review see Meade, 2019 ). In T. brucei , this Ca 2+ ATPase has high affinity for Ca 2+ and is sensible to vanadate and to low concentrations of thapsigargin (TG), a long known specific SERCA inhibitor ( Nolan et al., 1994 ).…”

Section: The First Order Er Functions In Trypanosomatidsmentioning

confidence: 99%

“…The differences in the susceptibility to TG have been attributed to distinct transmembrane sequences in the SERCA TG-binding site in these parasites ( Furuya et al, 2001 ). Molecular modelling indicates that TG or its analogues might be used as a potential drug against trypanosomes ( Pérez-Gordones et al, 2015 ). In L. amazonensis , a Ca2+-ATPase LmAA1 is located in the ER and act as a virulence factor, i.e., strains overexpressing LmMA1were more infective in both mouse and in vitro macrophage infection experiments ( Rodriguez et al, 2002 ).…”

Section: The First Order Er Functions In Trypanosomatidsmentioning

confidence: 99%

The endoplasmic reticulum of trypanosomatids: An unrevealed road for chemotherapy

Sandes

Figueiredo²

2022

Front. Cell. Infect. Microbiol.

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The endoplasmic reticulum (ER) of higher eukaryotic cells forms an intricate membranous network that serves as the main processing facility for folding and assembling of secreted and membrane proteins. The ER is a highly dynamic organelle that interacts with other intracellular structures, as well as endosymbiotic pathogenic and non-pathogenic microorganisms. A strict ER quality control (ERQC) must work to ensure that proteins entering the ER are folded and processed correctly. Unfolded or misfolded proteins are usually identified, selected, and addressed to Endoplasmic Reticulum-Associated Degradation (ERAD) complex. Conversely, when there is a large demand for secreted proteins or ER imbalance, the accumulation of unfolded or misfolded proteins activates the Unfold Protein Response (UPR) to restore the ER homeostasis or, in the case of persistent ER stress, induces the cell death. Pathogenic trypanosomatids, such as Trypanosoma cruzi, Trypanosoma brucei and Leishmania spp are the etiological agents of important neglected diseases. These protozoans have a complex life cycle alternating between vertebrate and invertebrate hosts. The ER of trypanosomatids, like those found in higher eukaryotes, is also specialized for secretion, and depends on the ERAD and non-canonical UPR to deal with the ER stress. Here, we reviewed the basic aspects of ER biology, organization, and quality control in trypanosomatids. We also focused on the unusual way by which T. cruzi, T. brucei, and Leishmania spp. respond to ER stress, emphasizing how these parasites’ ER-unrevealed roads might be an attractive target for chemotherapy.

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Presence of a thapsigargin-sensitive calcium pump in Trypanosoma evansi: Immunological, physiological, molecular and structural evidences

Cited by 9 publications

References 56 publications

Functional Innovation in the Evolution of the Calcium-Dependent System of the Eukaryotic Endoplasmic Reticulum

Functional Innovation in the Evolution of the Calcium-Dependent System of the Eukaryotic Endoplasmic Reticulum

Terpenes and Terpenoids Conjugated with BODIPYs: An Overview of Biological and Chemical Properties

The endoplasmic reticulum of trypanosomatids: An unrevealed road for chemotherapy

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