Localização genômica e subcelular dos membros da família de fosfatidilinositol quinases em Trypanosoma cruzi / Genomic and subcellular localization of the members of phosphatidylinositol kinase family in Trypanosoma cruzi

AUTOR(ES)
FONTE

IBICT - Instituto Brasileiro de Informação em Ciência e Tecnologia

DATA DE PUBLICAÇÃO

27/07/2011

RESUMO

The identification of signaling molecules and the elucidation of signal transduction processes of Trypanosoma cruzi are required for understanding the host-parasite interaction and physiological processes of the parasite. However, little is yet known about signal transduction and signaling pathways that occur in the parasite, since most efforts focused on signaling pathways that occur in the host cell. Our group recently identified a protein family of lipid kinases - the phosphatidylinositol kinases (PIKS) in the genome of the parasite. The PIKS molecules are evolutionarily conserved, they occur in all eukaryotic cells and are related to biological mechanisms essential for the cell, such as the organization of the cytoskeleton, cytokinesis, cell migration, signal transduction and cell survival. By using bioinformatics tools, the PIKS were classified into five different models (1-5) based on the presence of conserved domains. These genes were mapped on the chromosomes of two different isolates of T. cruzi (G and CL Brener). Surprisingly, the pattern of localization of all PIK genes chromosomal showed a significant polymorphism between the two isolates. By using fluorescence microscopy, six PIK proteins were located at the subcellular level. The subcellular localization of TcTOR1 and 2 (both Model 5) is completely different from that previously observed in Trypanosoma brucei. Unlike TbTOR1, TcTOR1 is excluded from the nucleus and is concentrated in the posterior punctated compartments that coincide with reservosomes, which was confirmed using anti-cruzipain. Reservosomes are endocytic organelles of epimastigotes of Trypanosoma cruzi that store proteins and lipids for future use. TcTOR2, unlike TbTOR2, is dispersed in the cytoplasm, concentrating around the location of TcTOR1. TOR1 and TOR2 have distinct patterns of localization, which is consistent with the regulation of cellular processes as part of two different complexes. Treatment with rapamycin inhibited the growth of epimastigotes, as well as promoted important morphological changes in the parasite. This result coincides with the fact that TOR2 and not TOR1 - is sensitive to rapamycin, which was previously demonstrated in T. brucei, and it may be a unique feature among trypanosomatids. Furthermore, overexpression of Model 1 (Class III PIK) in T. cruzi led to a reduction in the growth of the parasite when compared to control. The different infective forms of T. cruzi overexpressing the Model 1 showed a considerable variation in their rate of invasion into HeLa cells. These results indicate that Model 1 may play different roles in different infective forms of T. cruzi. The knowledge of these biomolecules at a molecular and cellular levels is a need for deeper understanding of the biology of the parasite and how to intervene in the progression of their life cycle and its relationship with the host cell. Notably, the PIK pathway has been widely acknowledged as an excellent target for drug discovery to combat this pathogen.

ASSUNTO(S)

trypanosoma cruzi fosfatidilinositol quinases proteína quinase microbiologia

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