Developmental Expression of a
            <i>Trypanosoma cruzi</i>
            Phosphoinositide-Specific Phospholipase C in Amastigotes and Stimulation of Host Phosphoinositide Hydrolysis

Martins, Vívian T.; Galizzi, Melina; Salto, María Laura; Docampo, Roberto; Moreno, Silvia N.J.

doi:10.1128/iai.00473-10

Cited by 17 publications

(8 citation statements)

References 25 publications

(33 reference statements)

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“…In conclusion, these works (Hashimoto et al , 2013; Huang et al , 2013) clearly established the presence of a functional IP 3 receptor in T. brucei and T. cruzi, and together with previous reports (Docampo and Pignataro, 1991; Moreno et al , 1992a; Moreno et al , 1992b; Furuya et al , 2000; Okura et al , 2005; de Paulo Martins et al , 2010; Martins et al , 2010), the function of a complete IP 3 /diacylglycerol pathway in trypanosomes.…”

Section: Intracellular Calcium Channels In Parasitic Protozoasupporting

confidence: 86%

“…Similar experiments were done with isolated acidocalcisomes resulting in significant Ca 2+ release by IP 3 (Huang et al , 2013). Previous attempts to show Ca 2+ release by IP 3 had been unsuccessful (Moreno et al , 1992a; Moreno et al , 1992b), which was difficult to explain considering that the parasites do have a phosphoinositide phospholipase C (PI-PLC) (Furuya et al , 2000; Okura et al , 2005; Martins et al , 2010), the enzyme that cleaves phosphatidylinositol 4,5-bisphosphate to generate diacylglycerol and IP 3 , and that IP 3 was detected in both T. cruzi (Moreno et al , 1992b) and T. brucei (Moreno et al , 1992a). When those experiments were done (1991–2) the presence of acidocalcisomes (Vercesi et al , 1994; Docampo et al , 1995) and an acidocalcisome vacuolar H + -PPase in trypanosomes were not known, as they were discovered much latter (Scott et al , 1998; Rodrigues et al , 1999).…”

Section: Intracellular Calcium Channels In Parasitic Protozoamentioning

confidence: 99%

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Intracellular calcium channels in protozoa

Docampo¹,

Moreno²,

Plattner³

2014

European Journal of Pharmacology

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Ca2+-signaling pathways and intracellular Ca2+ channels are present in protozoa. Ancient origin of inositol 1,4,5-trisphosphate receptors (IP3Rs) and other intracellular channels predates the divergence of animals and fungi as evidenced by their presence in the choanoflagellate Monosiga brevicollis, the closest known relative to metazoans. The first protozoan IP3R cloned, from the ciliate Paramecium, displays strong sequence similarity to the rat type 3 IP3R. This ciliate has a large number of IP3- and ryanodine(Ry)-like receptors in 6 subfamilies suggesting the evolutionary adaptation to local requirements for an expanding diversification of vesicle trafficking. IP3Rs have also been functionally characterized in trypanosomatids, where they are essential for growth, differentiation, and establishment of infection. The presence of the mitochondrial calcium uniporter (MCU) in a number of protozoa indicates that mitochondrial regulation of Ca2+ signaling is also an early appearance in evolution, and contributed to the discovery of the molecular nature of this channel in mammalian cells. There is only sequence evidence for the occurrence of two-pore channels (TPCs), transient receptor potential Ca2+ channels (TRPCs) and intracellular mechanosensitive Ca2+-channels in Paramecium and in parasitic protozoa.

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Section: Intracellular Calcium Channels In Parasitic Protozoasupporting

confidence: 86%

Section: Intracellular Calcium Channels In Parasitic Protozoamentioning

confidence: 99%

Intracellular calcium channels in protozoa

Docampo¹,

Moreno²,

Plattner³

2014

European Journal of Pharmacology

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“…Again, we only found TS associated to microvesicles rather than as a soluble protein. Thus, even if differentiating amastigotes shed PI-PLC [ 53 ], the enzymatic activity is not enough to quantitatively hydrolyze the TS GPI-anchor.…”

Section: Resultsmentioning

confidence: 99%

Sialic Acid Glycobiology Unveils Trypanosoma cruzi Trypomastigote Membrane Physiology

et al. 2016

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Trypanosoma cruzi, the flagellate protozoan agent of Chagas disease or American trypanosomiasis, is unable to synthesize sialic acids de novo. Mucins and trans-sialidase (TS) are substrate and enzyme, respectively, of the glycobiological system that scavenges sialic acid from the host in a crucial interplay for T. cruzi life cycle. The acquisition of the sialyl residue allows the parasite to avoid lysis by serum factors and to interact with the host cell. A major drawback to studying the sialylation kinetics and turnover of the trypomastigote glycoconjugates is the difficulty to identify and follow the recently acquired sialyl residues. To tackle this issue, we followed an unnatural sugar approach as bioorthogonal chemical reporters, where the use of azidosialyl residues allowed identifying the acquired sugar. Advanced microscopy techniques, together with biochemical methods, were used to study the trypomastigote membrane from its glycobiological perspective. Main sialyl acceptors were identified as mucins by biochemical procedures and protein markers. Together with determining their shedding and turnover rates, we also report that several membrane proteins, including TS and its substrates, both glycosylphosphatidylinositol-anchored proteins, are separately distributed on parasite surface and contained in different and highly stable membrane microdomains. Notably, labeling for α(1,3)Galactosyl residues only partially colocalize with sialylated mucins, indicating that two species of glycosylated mucins do exist, which are segregated at the parasite surface. Moreover, sialylated mucins were included in lipid-raft-domains, whereas TS molecules are not. The location of the surface-anchored TS resulted too far off as to be capable to sialylate mucins, a role played by the shed TS instead. Phosphatidylinositol-phospholipase-C activity is actually not present in trypomastigotes. Therefore, shedding of TS occurs via microvesicles instead of as a fully soluble form.

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“…It has been previously shown in various types of cells that elevation of IP 3 production, which release Ca 2+ from intracellular stores [24,69] [69] and a robust Ca 2+ release upon exposure to IP 3 BM-, ET-1-, or BK [69]. The elevated intracellular [IP 3 ] can have two possible sources i) the plasma membrane of parasites in intracellular forms, such as amastigotes [70] and ii) IP 3 derived from the plasma membrane of the host changes due to changes in IP 3 synthesis and/or degradation [71,72]. Furthermore, an elevated [IP 3 ] i may provoke an increase in Ca efflux from the SR, which could end in a depletion of intraluminal sarcoplasmic reticulum Ca 2+ content [24,73].…”

Section: Plos Neglected Tropical Diseasesmentioning

confidence: 99%

Increases in [IP3]i aggravates diastolic [Ca2+] and contractile dysfunction in Chagas’ human cardiomyocytes

Mijares

Espinosa²,

Adams

et al. 2020

PLoS Negl Trop Dis

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Chagas cardiomyopathy is the most severe manifestation of human Chagas disease and represents the major cause of morbidity and mortality in Latin America. We previously demonstrated diastolic Ca 2+ alterations in cardiomyocytes isolated from Chagas' patients to different degrees of cardiac dysfunction. In addition, we have found a significant elevation of diastolic [Na + ] d in Chagas' cardiomyocytes (FCII>FCI) that was greater than control. Exposure of cardiomyocytes to agents that enhance inositol 1,4,5 trisphosphate (IP 3) generation or concentration like endothelin (ET-1) or bradykinin (BK), or membrane-permeant myoinositol 1,4,5-trisphosphate hexakis(butyryloxy-methyl) esters (IP 3 BM) caused an elevation in diastolic [Ca 2+ ] ([Ca 2+ ] d) that was always greater in cardiomyocytes from Chagas' than non-Chagas' subjects, and the magnitude of the [Ca 2+ ] d elevation in Chagas' cardiomyocytes was related to the degree of cardiac dysfunction. Incubation with xestospongin-C (Xest-C), a membrane-permeable selective blocker of the IP 3 receptors (IP 3 Rs), significantly reduced [Ca 2+ ] d in Chagas' cardiomyocytes but did not have a significant effect on non-Chagas' cells. The effects of ET-1, BK, and IP 3 BM on [Ca 2+ ] d were not modified by the removal of extracellular [Ca 2+ ] e. Furthermore, cardiomyocytes from Chagas' patients had a significant decrease in the sarcoplasmic reticulum (SR) Ca 2+ content compared to control (Control>F-CI>FCII), a higher intracellular IP 3 concentration ([IP 3 ] i) and markedly depressed contractile properties compared to control cardiomyocytes. These results provide additional and convincing support about the implications of IP 3 in the pathogenesis of Chagas cardiomyopathy in patients at different stages of chronic infection. Additionally, these findings open the door for novel therapeutic strategies oriented to improve cardiac function and quality of life of individuals suffering from chronic Chagas cardiomyopathy (CC).

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Developmental Expression of a Trypanosoma cruzi Phosphoinositide-Specific Phospholipase C in Amastigotes and Stimulation of Host Phosphoinositide Hydrolysis

Cited by 17 publications

References 25 publications

Intracellular calcium channels in protozoa

Intracellular calcium channels in protozoa

Sialic Acid Glycobiology Unveils Trypanosoma cruzi Trypomastigote Membrane Physiology

Increases in [IP3]i aggravates diastolic [Ca2+] and contractile dysfunction in Chagas’ human cardiomyocytes

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