Proteome changes upon modulation of eIF2α phosphorylation in Trypanosoma cruzi epimastigotes

Trypanosomatids regulate gene expression mainly at the post-transcriptional level through processing, exporting and stabilizing mRNA and control of translation. In most eukaryotes, protein synthesis is regulated by phosphorylation of eukaryotic initiation factor 2 (eIF2) at serine 51. Phosphorylation halts overall translation by decreasing availability of initiator tRNAmet to form translating ribosomes. In trypanosomatids the N-terminus of eIF2α is extended with threonine 169 the homologous phosphorylated residue and eIF2α phosphorylation increases in proliferative intracellular forms prior to differentiation into trypomastigotes. Here we analyse the proteome changes in epimatigotes upon eIF2αT169A mutation and knock-out of the kinase TcK11, an ortolog of the general control nonderepressible 2 (GCN2)kinases which have been implicated in eukaryotic eIF2α ser51 phosphorylation.