Mattos Eliciane C, Tonelli Renata R, Colli Walter, Alves Maria Julia M
Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Av. Prof. Lineu Prestes 748, 05508-900, Cidade Universitária, São Paulo, Brazil.
Subcell Biochem. 2014;74:151-80. doi: 10.1007/978-94-007-7305-9_7.
Trypanosoma cruzi strains show distinctive characteristics as genetic polymorphism and infectivity. Large repertoires of molecules, such as the Gp85 glycoproteins, members of the Gp85/Trans-sialidase superfamily, as well as multiple signaling pathways, are associated with invasion of mammalian cells by the parasite. Due to the large number of expressed members, encoded by more than 700 genes, the research focused on this superfamily conserved sequences is discussed. Binding sites to laminin have been identified at the N-terminus of the Gp85 molecules. Interestingly, the T. cruzi protein phosphorylation profile is changed upon parasite binding to laminin (or fibronectin), particularly the cytoskeletal proteins such as those from the paraflagellar rod and the tubulins, which are both markedly dephosphorylated. Detailed analysis of the signaling cascades triggered upon T. cruzi binding to extracellular matrix (ECM) proteins revealed the involvement of the MAPK/ERK pathway in this event. At the C-terminus, the conserved FLY sequence is a cytokeratin-binding domain and is involved in augmented host cell invasion in vitro and high levels of parasitemia in vivo. FLY, which is associated to tissue tropism and preferentially binds to the heart vasculature may somehow be correlated with the severe cardiac form, an important clinical manifestation of chronic Chagas' disease.
克氏锥虫菌株表现出独特的特征，如基因多态性和感染性。大量分子，如Gp85糖蛋白、Gp85/转唾液酸酶超家族成员以及多种信号通路，与该寄生虫对哺乳动物细胞的侵袭有关。由于由700多个基因编码的表达成员数量众多，因此对该超家族保守序列的研究进行了讨论。在Gp85分子的N端已鉴定出与层粘连蛋白的结合位点。有趣的是，当寄生虫与层粘连蛋白（或纤连蛋白）结合时，克氏锥虫的蛋白质磷酸化谱会发生变化，特别是细胞骨架蛋白，如副鞭毛杆蛋白和微管蛋白，它们都会明显去磷酸化。对克氏锥虫与细胞外基质（ECM）蛋白结合后触发的信号级联反应的详细分析揭示了MAPK/ERK途径参与了这一事件。在C端区域，保守的FLY序列是一个细胞角蛋白结合结构域，参与体外增强宿主细胞侵袭和体内高水平的寄生虫血症。与组织嗜性相关并优先结合心脏血管系统的FLY可能在某种程度上与严重心脏型有关联，这是慢性恰加斯病的一种重要临床表现。
