NDLI: Intracellular Eukaryotic Parasites Have a Distinct Unfolded Protein Response

Content Provider	PubMed Central
Author	Gosline, Sara J. C. Nascimento, Mirna Mccall, Laura-isobel Zilberstein, Dan Thomas, David Y. Greg, Matlashewski Hallett, Michael
Editor	Heussler, Volker Theo
Abstract	Insult to the endoplasmic reticulum (ER) activates the Unfolded Protein Response (UPR), a set of signaling pathways that protect the cell from the potential damage caused by improperly folded proteins. Accumulation of misfolded proteins in the ER lumen initiates a series of signal transduction events via activation of three transmembrane ER proteins: Ire1, Atf6 and PERK. Activation of these proteins results in the transcriptional up-regulation of the components of the folding, trafficking and degradation machinery in the ER. PERK further reduces the load on the ER via the phosphorylation of eIF2α, attenuating general protein translation. It is believed that the UPR evolved as a transcriptional response that up-regulates protein folding machinery in the ER and later gained the ability to decrease ER load by attenuating general protein translation in metazoa. However, our in silico analyses of protozoan parasites revealed an absence of proteins involved in the transcriptionally mediated UPR and the presence of both PERK and its target eIF2α. Consistent with these observations, stimulation of the UPR in Leishmania donovani identified an absence of up-regulation of the ER chaperone BiP, the canonical ER chaperone modulated by the UPR in higher eukaryotes, while exhibiting increased phosphorylation of eIF2α which has been shown to attenuate protein translation. We further observed that L. donovani is more sensitive to UPR inducing agents than host macrophages, suggesting that the less evolved stress response could provide a new avenue for therapeutic treatment of parasitic infections.
Related Links	http://dx.doi.org/10.1371/journal.pone.0019118
Starting Page	19118
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	4
Volume Number	6
Language	English
Publisher	Public Library of Science
Publisher Date	2011-04-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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