Artículo

Schoijet, A.C.; Miranda, K.; Girard-Dias, W.; De Souza, W.; Flawia, M.M.; Torres, H.N.; Docampo, R.; Alonso, G.D. "A Trypanosoma cruzi phosphatidylinositol 3-kinase (TcVps34) is involved in osmoregulation and receptor-mediated endocytosis" (2008) Journal of Biological Chemistry. 283(46):31541-31550
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Abstract:

Trypanosoma cruzi, the etiological agent of Chagas disease, has the ability to respond to a variety of environmental changes during its life cycle both in the insect vector and in the vertebrate host. Because regulation of transcription initiation seems to be nonfunctional in this parasite, it is important to investigate other regulatory mechanisms of adaptation. Regulatory mechanisms at the level of signal transduction pathways involving phosphoinositides are good candidates for this purpose. Here we report the identification of the first phosphatidylinositol 3-kinase (PI3K) in T. cruzi, with similarity with its yeast counterpart, Vps34p. TcVps34 specifically phosphorylates phosphatidylinositol to produce phosphatidylinositol 3-phosphate, thus confirming that it belongs to class III PI3K family. Overexpression of TcVps34 resulted in morphological and functional alterations related to vesicular trafficking. Although inhibition of TcVps34 with specific PI3K inhibitors, such as wortmannin and LY294,000, resulted in reduced regulatory volume decrease after hyposmotic stress, cells overexpressing this enzyme were resistant to these inhibitors. Furthermore, these cells were able to recover their original volume faster than wild type cells when they were submitted to severe hyposmotic stress. In addition, in TcVps34-overexpressing cells, the activities of vacuolar-H+-ATPase and vacuolar H+- pyrophosphatase were altered, suggesting defects in the acidification of intracellular compartments. Furthermore, receptor-mediated endocytosis was partially blocked although fluid phase endocytosis was not affected, confirming a function for TcVps34 in membrane trafficking. Taken together, these results strongly support that TcVps34 plays a prominent role in vital processes for T. cruzi survival such as osmoregulation, acidification, and vesicular trafficking. © 2008 by The American Society for Biochemistry and Molecular Biology, Inc.

Registro:

Documento: Artículo
Título:A Trypanosoma cruzi phosphatidylinositol 3-kinase (TcVps34) is involved in osmoregulation and receptor-mediated endocytosis
Autor:Schoijet, A.C.; Miranda, K.; Girard-Dias, W.; De Souza, W.; Flawia, M.M.; Torres, H.N.; Docampo, R.; Alonso, G.D.
Filiación:Instituto de Investigaciones en Ingeniería Genética Y Biología Molecular, Consejo Nacional de Investigaciones Científicas Y Técnicas, Universidad de Buenos Aires, Vuelta de Obligado 2490 (1428), Buenos Aires, Argentina
Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
Center for Tropical and Emerging Global Diseases, Dept. of Cellular Biology, University of Georgia, Athens, GA 30602, United States
Instituto de Investigaciones en Ingenieria Genetica Y Biologia Molecular (INGEBI-CONICET), Vuelta de Obligado 2490 (1428), Buenos Aires, Argentina
Palabras clave:Cell membranes; Chemical reactions; Enzyme activity; Enzyme inhibition; Life cycle; Phospholipids; Phosphoric acid; Signal transduction; Chagas diseases; Environmental changes; Etiological agents; Intracellular compartments; Membrane trafficking; Osmoregulation; Overexpressing cells; Overexpression; Phosphatidylinositol; Phosphoinositides; Pyrophosphatase; Regulation of transcriptions; Regulatory mechanisms; Regulatory volume decreases; Signal transduction pathways; Trypanosoma cruzi; Vesicular trafficking; Wild types; Wortmannin; Laws and legislation; adenosine triphosphatase; ly 294000; phosphatidylinositol 3 kinase; phosphatidylinositol 3 kinase inhibitor; unclassified drug; wortmannin; acidification; article; cell migration; cell vacuole; cell volume; cellular distribution; cellular stress response; endocytosis; enzyme assay; enzyme inhibition; enzyme specificity; epimastigote; gene overexpression; nonhuman; nucleotide sequence; osmoregulation; priority journal; protein family; protein function; protein phosphorylation; sequence analysis; structural homology; survival time; tonoplast; Trypanosoma cruzi; wild type; yeast; 1-Phosphatidylinositol 3-Kinase; Animals; Cloning, Molecular; Endocytosis; Gene Expression Regulation, Enzymologic; Inorganic Pyrophosphatase; Microscopy, Electron, Scanning; Microscopy, Electron, Transmission; Molecular Sequence Data; Phenotype; Protein Kinase Inhibitors; Proton-Translocating ATPases; Saccharomyces cerevisiae; Trypanosoma cruzi; Water-Electrolyte Balance; Hexapoda; Trypanosoma cruzi; Vertebrata
Año:2008
Volumen:283
Número:46
Página de inicio:31541
Página de fin:31550
DOI: http://dx.doi.org/10.1074/jbc.M801367200
Título revista:Journal of Biological Chemistry
Título revista abreviado:J. Biol. Chem.
ISSN:00219258
CODEN:JBCHA
CAS:adenosine triphosphatase, 37289-25-1, 9000-83-3; phosphatidylinositol 3 kinase, 115926-52-8; wortmannin, 19545-26-7; 1-Phosphatidylinositol 3-Kinase, EC 2.7.1.137; Inorganic Pyrophosphatase, EC 3.6.1.1; Protein Kinase Inhibitors; Proton-Translocating ATPases, EC 3.6.3.14
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00219258_v283_n46_p31541_Schoijet

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Citas:

---------- APA ----------
Schoijet, A.C., Miranda, K., Girard-Dias, W., De Souza, W., Flawia, M.M., Torres, H.N., Docampo, R.,..., Alonso, G.D. (2008) . A Trypanosoma cruzi phosphatidylinositol 3-kinase (TcVps34) is involved in osmoregulation and receptor-mediated endocytosis. Journal of Biological Chemistry, 283(46), 31541-31550.
http://dx.doi.org/10.1074/jbc.M801367200
---------- CHICAGO ----------
Schoijet, A.C., Miranda, K., Girard-Dias, W., De Souza, W., Flawia, M.M., Torres, H.N., et al. "A Trypanosoma cruzi phosphatidylinositol 3-kinase (TcVps34) is involved in osmoregulation and receptor-mediated endocytosis" . Journal of Biological Chemistry 283, no. 46 (2008) : 31541-31550.
http://dx.doi.org/10.1074/jbc.M801367200
---------- MLA ----------
Schoijet, A.C., Miranda, K., Girard-Dias, W., De Souza, W., Flawia, M.M., Torres, H.N., et al. "A Trypanosoma cruzi phosphatidylinositol 3-kinase (TcVps34) is involved in osmoregulation and receptor-mediated endocytosis" . Journal of Biological Chemistry, vol. 283, no. 46, 2008, pp. 31541-31550.
http://dx.doi.org/10.1074/jbc.M801367200
---------- VANCOUVER ----------
Schoijet, A.C., Miranda, K., Girard-Dias, W., De Souza, W., Flawia, M.M., Torres, H.N., et al. A Trypanosoma cruzi phosphatidylinositol 3-kinase (TcVps34) is involved in osmoregulation and receptor-mediated endocytosis. J. Biol. Chem. 2008;283(46):31541-31550.
http://dx.doi.org/10.1074/jbc.M801367200