GCN2-Like Kinase Modulates Stress Granule Formation During Nutritional Stress in Trypanosoma cruzi

@article{Malvezzi2020GCN2LikeKM,
  title={GCN2-Like Kinase Modulates Stress Granule Formation During Nutritional Stress in Trypanosoma cruzi},
  author={Amaranta Muniz Malvezzi and Mirella {\'A}rico and Normanda Souza-Melo and Gregory Pedroso dos Santos and Paula Bittencourt-Cunha and Fab{\'i}ola Barbi{\'e}ri Holetz and Sergio Schenkman},
  journal={Frontiers in Cellular and Infection Microbiology},
  year={2020},
  volume={10}
}
The integrated stress response in eukaryotic cells is an orchestrated pathway that leads to eukaryotic Initiation Factor 2 alpha subunit (eIF2α) phosphorylation at ser51 and ultimately activates pathways to mitigate cellular damages. Three putative kinases (Tck1, Tck2, and Tck3) are found in the Trypanosoma cruzi genome, the flagellated parasite that causes Chagas disease. These kinases present similarities to other eukaryotic eIF2α kinases, exhibiting a typical insertion loop in the kinase… Expand
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References

SHOWING 1-10 OF 83 REFERENCES
GCN2-like eIF2α kinase manages the amino acid starvation response in Toxoplasma gondii.
TLDR
It is suggested that Toxoplasma GCN2-like kinases TgIF2K-C and Tg IF2k-D evolved to have distinct roles in adapting to changes in the parasite's environment. Expand
A GCN2-Like eIF2α Kinase (LdeK1) of Leishmania donovani and Its Possible Role in Stress Response
TLDR
It is proposed that global translational regulation by activation of LdeK1 followed by eIF2α phosphorylation and G1-arrest during nutrient starvation in the gut of sandfly vector could be one of the mechanisms to retool the cellular machinery required for metacyclogenesis of Leishmania promastigotes. Expand
A GCN2-Like Eukaryotic Initiation Factor 2 Kinase Increases the Viability of Extracellular Toxoplasma gondii Parasites
TLDR
These studies suggest that eIF2α phosphorylation and translational control are an important mechanism by which vulnerable extracellular parasites protect themselves while searching for a new host cell. Expand
Regulation of arginine transport by GCN2 eIF2 kinase is important for replication of the intracellular parasite Toxoplasma gondii
TLDR
This work has discovered that the integrated stress response (ISR) is induced in host cells infected with Toxoplasma, and establishes that the parasite usurps the host cell ISR to help secure nutrients that it needs for parasite replication. Expand
A Membrane-bound eIF2 Alpha Kinase Located in Endosomes Is Regulated by Heme and Controls Differentiation and ROS Levels in Trypanosoma cruzi
TLDR
Heme is a key factor for the growth control and differentiation through regulation of an unusual type of eIF2α kinase in T. cruzi, and it is found that heme binds specifically to the catalytic domain of the kinase, inhibiting its activity. Expand
Protein Synthesis Attenuation by Phosphorylation of eIF2α Is Required for the Differentiation of Trypanosoma cruzi into Infective Forms
TLDR
The role of eIF2α phosphorylation as a key step in T. cruzi differentiation is defined, which is critical for parasite differentiation since the overexpression of the mutant eif2α in epimastigotes abolished metacyclogenesis. Expand
Keeping the eIF2 alpha kinase Gcn2 in check.
TLDR
This review provides a critical evaluation of the current knowledge on mechanisms controlling Gcn2 activation or activity and suggests that the current level of knowledge on these mechanisms is inadequate. Expand
Novel Membrane-Bound eIF2α Kinase in the Flagellar Pocket of Trypanosoma brucei
TLDR
It is shown here that TbeIF2K2 is a transmembrane glycoprotein expressed both in procyclic and in bloodstream forms, and this is the first membrane-associated eIF2α kinase described in unicellular eukaryotes. Expand
PfeIK1, a eukaryotic initiation factor 2α kinase of the human malaria parasite Plasmodium falciparum, regulates stress-response to amino-acid starvation
TLDR
This study strongly suggests that a mechanism for versatile regulation of translation by several kinases with a similar catalytic domain but distinct regulatory domains, is conserved in P. falciparum. Expand
Protein and mRNA content of TcDHH1‐containing mRNPs in Trypanosoma cruzi
TLDR
The results suggest that mRNPs containing TcDHH1 are involved in mRNA metabolism, regulating the expression of at least epimastigote‐specific genes in the trypanosomatids life cycle. Expand
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