The ER chaperone PfGRP170 is essential for asexual development and is linked to stress response in malaria parasites.

Details

• Alternative Title:
  Cell Microbiol
• Personal Author:
  Kudyba, Heather M. ; Cobb, David W. ; Fierro, Manuel A. ; Florentin, Anat ; Ljolje, Dragan ; Singh, Balwan ; Lucchi, Naomi W. ; Muralidharan, Vasant
• Description:
  The vast majority of malaria mortality is attributed to one parasite species: Plasmodium falciparum. Asexual replication of the parasite within the red blood cell is responsible for the pathology of the disease. In Plasmodium, the endoplasmic reticulum (ER) is a central hub for protein folding and trafficking as well as stress response pathways. In this study, we tested the role of an uncharacterised ER protein, PfGRP170, in regulating these key functions by generating conditional mutants. Our data show that PfGRP170 localises to the ER and is essential for asexual growth, specifically required for proper development of schizonts. PfGRP170 is essential for surviving heat shock, suggesting a critical role in cellular stress response. The data demonstrate that PfGRP170 interacts with the Plasmodium orthologue of the ER chaperone, BiP. Finally, we found that loss of PfGRP170 function leads to the activation of the Plasmodium eIF2α kinase, PK4, suggesting a specific role for this protein in this parasite stress response pathway.
• Subjects:
  Article EIF-2 Kinase Endoplasmic Reticulum Endoplasmic Reticulum Stress Erythrocytes Heat-Shock Response HSP70 Heat-Shock Proteins Humans Mass Spectrometry Molecular Chaperones Mutation Plasmodium Falciparum Protozoan Proteins Schizonts

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• Source:
  Cell Microbiol. 21(9):e13042
• Pubmed ID:
  31087747
• Pubmed Central ID:
  PMC6699899
• Document Type:
  Journal Article
• Funding:
  18POST34080315/American Heart Association Postdoctoral Fellowship/International ; T32 AI060546/AI/NIAID NIH HHS/United States ; T32AI060546/National Institute of Allergy and Infectious Diseases/International ; R00AI099156/National Institute of Allergy and Infectious Diseases/International ; R01 AI130139/AI/NIAID NIH HHS/United States ; R00 AI099156/AI/NIAID NIH HHS/United States ; CDC-UGA Seed Award/University of Georgia/International ; R01AI130139/National Institute of Allergy and Infectious Diseases/International
• Volume:
  21
• Issue:
  9
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:cf18736609abbb22c4c3fbc50dd311681a1569ecdbd367db09695da91c72ded8
• Download URL:
  https://stacks.cdc.gov/view/cdc/80786/cdc_80786_DS1.pdf
• File Type:
  [PDF - 1.45 MB ]