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Phenotypic Analysis of Rodent Malaria Parasite Asexual and Sexual Blood Stages and Mosquito Stages
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The endoplasmic reticulum chaperone PfGRP170 is essential for asexual development and is linked to stress response in

Heather M Kudyba1,2, David W Cobb1,2, Manuel A Fierro1,2

  • 1Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, Georgia.

Cellular Microbiology
|May 16, 2019
PubMed

Insights

PfGRP170, an endoplasmic reticulum (ER) protein in Plasmodium falciparum malaria parasites, is essential for asexual growth and surviving heat shock. Its loss activates a key stress response pathway, impacting parasite survival.

Area of Science:

  • Parasitology
  • Molecular Biology
  • Cellular Biology

Background:

  • Malaria mortality is predominantly caused by Plasmodium falciparum.
  • Parasite-induced red blood cell pathology stems from asexual replication.
  • The endoplasmic reticulum (ER) is crucial for protein homeostasis and stress responses in Plasmodium.

Purpose of the Study:

  • To investigate the function of the uncharacterized ER protein PfGRP170 in Plasmodium falciparum.
  • To determine PfGRP170's role in protein folding, trafficking, and stress response pathways.

Main Methods:

  • Generation of conditional PfGRP170 mutants in Plasmodium.
  • Localization studies of PfGRP170 within the parasite.
  • Assessment of asexual growth and heat shock survival.
  • Co-immunoprecipitation to identify interacting proteins.
  • Analysis of downstream stress response pathway activation.

Main Results:

  • PfGRP170 localizes to the ER and is essential for asexual parasite growth, particularly schizont development.
  • The protein is critical for parasite survival under heat shock conditions.
  • PfGRP170 interacts with BiP, a Plasmodium ER chaperone.
  • Loss of PfGRP170 function leads to activation of the eIF2α kinase, PK4.

Conclusions:

  • PfGRP170 plays a vital role in Plasmodium falciparum asexual development and cellular stress response.
  • The protein is involved in ER protein homeostasis and interacts with BiP.
  • PfGRP170 is a key component of the parasite's response to ER stress, involving the PK4 pathway.
Keywords:
Plasmodium falciparumendoplasmic reticulummalariaparasitology

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