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|Title:||A protein phosphatase 1 gamma (PP1 gamma) of the human protozoan parasite Trichomonas vaginalis is involved in proliferation and cell attachment to the host cell|
Orrego, Patricio R.
Castillo, Juan L.
Silveira, Jose Franco da [UNIFESP]
Cordero, Esteban [UNIFESP]
Araya, Jorge E.
Universidade Federal de São Paulo (UNIFESP)
Univ Santa Ursula
Protein phosphatase 1
Expression and genomic organisation
|Citation:||International Journal for Parasitology. Oxford: Elsevier B.V., v. 42, n. 8, p. 715-727, 2012.|
|Abstract:||In this work, evidence for a critical role of Trichomonas vaginalis protein phosphatase 1 gamma (TvPP1 gamma) in proliferation and attachment of the parasite to the mammalian cell is provided. Firstly, proliferation and attachment of T. vaginalis parasites to HeLa cells was blocked by calyculin A (CA), a potent PP1 inhibitor. Secondly, it was demonstrated that the enzyme activity of native and recombinant TvPP1 gamma proteins was inhibited by CA. Thirdly, reverse genetic studies confirmed that antisense oligonucleotides targeted to PP1 gamma but not PP1 alpha or beta inhibited proliferation and attachment of trichomonads CA-treated parasites underwent cytoskeletal modifications, including a lack of axostyle typical labelling, suggesting that cytoskeletal phosphorylation could be regulated by a CA-sensitive phosphatase where the role of PP1 gamma could not be ruled out. Analysis of subcellular distribution of TvPP1 gamma by cell fractionation and electron microscopy demonstrated the association between TvPP1 gamma and the cytoskeleton. the expression of adhesins, AP120 and AP65, at the cell surface was also inhibited by CA. the concomitant inhibition of expression of adhesins and changes in the cytoskeleton in CA-treated parasites suggest a specific role for PP1 gamma - dependent dephosphorylation in the early stages of the host-parasite interaction. Molecular modelling of TvPP1 gamma showed the conservation of residues critical for maintaining proper folding into the gross structure common to PP1 proteins. Taken together, these results suggest that TvPP1 gamma could be considered a potential novel drug target for treatment of trichomoniasis. (C) 2012 Australian Society for Parasitology Inc. Published by Elsevier B.V. All rights reserved.|
|Appears in Collections:||Em verificação - Geral|
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