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The acidocalcisome inositol-1,4,5-trisphosphate receptor of Trypanosoma brucei is stimulated by luminal polyphosphate hydrolysis products

Donna Huber on May 28, 2019

Acidocalcisomes are acidic calcium stores rich in polyphosphate (polyP) and are present in trypanosomes and also in a diverse range of other organisms. Ca2+ is released from these organelles through a channel, inositol 1,4,5-trisphosphate receptor (TbIP3R), which is essential for growth and infectivity of the parasite Trypanosoma brucei. However, the mechanism by which TbIP3R controls …

Nucleocytoplasmic O-glycosylation in protists

Donna Huber on May 22, 2019

O-Glycosylation is an increasingly recognized modification of intracellular proteins in all kingdoms of life, and its occurrence in protists has been investigated to understand its evolution and its roles in the virulence of unicellular pathogens. We focus here on two kinds of glycoregulation found in unicellular eukaryotes: one is a simple O-fucose modification of dozens if …

The Vacuolar Zinc Transporter TgZnT Protects Toxoplasma gondii from Zinc Toxicity

Donna Huber on May 22, 2019

Zinc (Zn2+) is the most abundant biological metal ion aside from iron and is an essential element in numerous biological systems, acting as a cofactor for a large number of enzymes and regulatory proteins. Zn2+ must be tightly regulated, as both the deficiency and overabundance of intracellular free Zn2+ are harmful to cells. Zn2+ transporters (ZnTs) play important …

Refugia and anthelmintic resistance: Concepts and challenges

Donna Huber on May 17, 2019

Anthelmintic resistance is a threat to global food security. In order to alleviate the selection pressure for resistance and maintain drug efficacy, management strategies increasingly aim to preserve a proportion of the parasite population in ‘refugia’, unexposed to treatment. While persuasive in its logic, and widely advocated as best practice, evidence for the ability of …

Functional analysis and importance for host cell infection of the Ca2+-conducting subunits of the mitochondrial calcium uniporter of Trypanosoma cruzi

Donna Huber on May 15, 2019

We report here that Trypanosoma cruzi, the etiologic agent of Chagas disease, possesses two unique paralogs of the mitochondrial calcium uniporter complex TcMCU subunit that we named TcMCUc, and TcMCUd. The predicted structure of the proteins indicates that, as that predicted for the TcMCU and TcMCUb paralogs, they are composed of two helical membrane-spanning domains, and contain a WDXXEPXXY motif. Overexpression of each gene led …

The Toxoplasma Vacuolar H+-ATPase Regulates Intracellular pH and Impacts the Maturation of Essential Secretory Proteins

Donna Huber on May 14, 2019

Vacuolar-proton ATPases (V-ATPases) are conserved complexes that couple the hydrolysis of ATP to the pumping of protons across membranes. V-ATPases are known to play diverse roles in cellular physiology. We studied the Toxoplasma gondiiV-ATPase complex and discovered a dual role of the pump in protecting parasites against ionic stress and in the maturation of secretory proteins in …

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

Donna Huber on May 14, 2019

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 …

Toll family members bind multiple Spätzle proteins and activate antimicrobial peptide gene expression in Drosophila

Donna Huber on May 14, 2019

This illustration depicts a dorsal view of the “common” fruit fly, or “vinegar” fly, Drosophila melanogaster.Courtesy of Public Health Image Library The Toll signaling pathway in Drosophila melanogaster regulates several immune-related functions, including the expression of antimicrobial peptide (AMP) genes. The canonical Toll receptor (Toll-1) is activated by the cytokine Spätzle (Spz-1), but Drosophila encodes …

MICU1 and MICU2 Play an Essential Role in Mitochondrial Ca2+ Uptake, Growth, and Infectivity of the Human Pathogen Trypanosoma cruzi

Donna Huber on May 7, 2019

The mitochondrial Ca2+ uptake in trypanosomatids, which belong to the eukaryotic supergroup Excavata, shares biochemical characteristics with that of animals, which, together with fungi, belong to the supergroup Opisthokonta. However, the composition of the mitochondrial calcium uniporter (MCU) complex in trypanosomatids is quite peculiar, suggesting lineage-specific adaptations. In this work, we used Trypanosoma cruzi to study the role …

Distinct amino acid and lipid perturbations characterize acute versus chronic malaria

Donna Huber on May 2, 2019

Chronic malaria is a major public health problem and significant challenge for disease eradication efforts. Despite its importance, the biological factors underpinning chronic malaria are not fully understood. Recent studies have shown that host metabolic state can influence malaria pathogenesis and transmission, but its role in chronicity is not known. Here, with the goal of …

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