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Understanding the Development of Compensatory Pathways in a Mutant Malaria Parasite Harbouring Hypomorphic Allele of Plant-Like Kinases
Published on: November 22, 2024
The host targeting motif in exported Plasmodium proteins is cleaved in the parasite endoplasmic reticulum
Andrew R Osborne1, Kaye D Speicher, Pamela A Tamez
1Center for Rare and Neglected Diseases, University of Notre Dame, 103 Galvin Life Sciences, South Bend, IN 46556, USA.
Abstract:
During the blood stage of its lifecycle, the malaria parasite resides and replicates inside a membrane vacuole within its host cell, the human erythrocyte. The parasite exports many proteins across the vacuole membrane and into the host cell cytoplasm. Most exported proteins are characterized by the presence of a host targeting (HT) motif, also referred to as a Plasmodium export element (PEXEL), which corresponds to the consensus sequence RxLxE/D/Q. During export the HT motif is cleaved by an unknown protease. Here, we generate parasite lines expressing HT motif containing proteins that are localized to different compartments within the parasite or host cell. We find that the HT motif in a protein that is retained in the parasite endoplasmic reticulum is cleaved and N-acetylated as efficiently as a protein that is exported. This shows that cleavage of the HT motif occurs early in the secretory pathway, in the parasite endoplasmic reticulum.
Insights
The malaria parasite
Area of Science:
- Malariology
- Molecular Parasitology
- Cell Biology
Background:
- The malaria parasite (Plasmodium) exports proteins to its host cell, the human erythrocyte, during its blood stage.
- Many exported proteins utilize a conserved Plasmodium export element (PEXEL) motif for translocation.
- The PEXEL motif is cleaved by an unknown protease during protein export.
Purpose of the Study:
- To investigate the timing and location of PEXEL motif cleavage.
- To determine if PEXEL cleavage is dependent on protein export into the host cell.
Main Methods:
- Generated Plasmodium parasite lines expressing PEXEL-containing proteins targeted to different cellular compartments.
- Analyzed PEXEL motif cleavage and N-acetylation in proteins retained within the parasite versus those exported.
Main Results:
- Cleavage and N-acetylation of the PEXEL motif occurred efficiently even in proteins retained within the parasite's endoplasmic reticulum.
- This indicates that PEXEL cleavage is not solely dependent on the export process into the host cell.
Conclusions:
- PEXEL motif cleavage occurs early in the parasite's secretory pathway, specifically within the endoplasmic reticulum.
- This finding provides crucial insights into the mechanism of protein export in malaria parasites.
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