Phosphorylation of eIF2α on Threonine 169 is not required for Trypanosoma brucei cell cycle arrest during differentiation

Carla Cristi D.C. Avila, Lori Peacock, Fabricio Castro Machado, Wendy C Gibson, Sergio Schenkman, Mark Carrington, Beatriz A. Castilho

Research output: Contribution to journalArticle (Academic Journal)peer-review

6 Citations (Scopus)
244 Downloads (Pure)

Abstract

The trypanosome life cycle consists of a series of developmental forms each adapted to an environment in the relevant insect and/or mammalian host. The differentiation process from the mammalian bloodstream form to the insect-midgut procyclic form in Trypanosoma brucei occurs in two steps in vivo. First proliferating ‘slender' bloodstream forms differentiate to non-dividing ‘stumpy' forms arrested in G1. Second, in response to environmental cues, stumpy bloodstream forms re-enter the cell cycle and start to proliferate as procyclic forms after a lag during which both cell morphology and gene expression are modified. Nearly all arrested cells have lower rates of protein synthesis when compared to the proliferating equivalent. In eukaryotes, one mechanism used to regulate the overall rate of protein synthesis involves phosphorylation of the alpha subunit of initiation factor eIF2 (eIF2α). The effect of eIF2α phosphorylation is to prevent the action of eIF2B, the guanine nucleotide exchange factor that activates eIF2 for the next rounds of initiation. To investigate the role of the phosphorylation of eIF2α in the life cycle of T. brucei, a cell line was made with a single eIF2α gene that contained the phosphorylation site, threonine 169, mutated to alanine. These cells were capable of differentiating from proliferating bloodstream form cells into arrested stumpy forms in mice and into procyclic forms in vitro and in tsetse flies. These results indicate that translation attenuation mediated by the phosphorylation of eIF2α on threonine 169 is not necessary for the cell cycle arrest associated with these differentiation processes.
Original languageEnglish
Pages (from-to)16-21
Number of pages6
JournalMolecular and Biochemical Parasitology
Volume205
Issue number1-2
Early online date17 Mar 2016
DOIs
Publication statusPublished - Mar 2016

Keywords

  • T. brucei
  • cell cycle arrest
  • differentiation
  • translation initiation
  • eIF2

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