O papel da fosforilação de tbeif2 no ciclo de vida de trypanosoma brucei

Résumé fourni par la source

The trypanosomes present processes of differentiation resulting from the different environments found in their insect vectors and mammalian hosts, probably representing stress situations. The adaptation to these environments depends on the differential gene expression. Trypanosomes have little transcriptional regulation, and it is believed that post-transcriptional regulation is the primary mechanism for controlling gene expression. Translational regulation should therefore be relevant in this differentiation process [1]. In eukaryotes, the modulation of the activity of the initiation factor eIF2 by phosphorylation of its alpha subunit (eIF2?) is crucial in determining the levels of translation in response to various stress situations, leading to lower overall levels of translation and triggering a recovery response [2]. In Trypanosoma brucei, the levels of protein synthesis differ in procyclic forms, blood "slender" and blood "stumpy" forms. The polissomal profiles of these forms indicate significant variations in translation initiation [3]. We have previously characterized the T. brucei eIF2? and described its three different eIF2? kinases [ 4 ] . To study the role of the phosphorylation of eIF2? in the biology of T. brucei, blood form parasites with the site of phosphorylation of eIF2? (Thr169) mutated to alanine were obtained. These cells were capable of differentiating into stumpy forms in mice, and in procyclic forms in vitro. The mutants were able to infect and differentiate to procyclics in tse-tse flies. Parasites with eIF2?Thr169Ala were more resistant to certain stress conditions.

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