Abstract
Trypanosoma cruzi is a protist parasite and the causative agent of American trypanosomiasis or Chagas disease. The parasite life cycle in its mammalian host includes an intracellular stage, and glycosylated proteins play a key role in host-parasite interaction facilitating adhesion, invasion and immune evasion. Here, we report that a Golgi-localized Mn2+-Ca2+/H+ exchanger of T. cruzi (TcGDT1) is required for efficient protein glycosylation, host cell invasion, and intracellular replication. The Golgi localization was determined by immunofluorescence and electron microscopy assays. TcGDT1 was able to complement the growth defect of Saccharomyces cerevisiae null mutants of its ortholog ScGDT1 but ablation of TcGDT1 by CRISPR/Cas9 did not affect the growth of the insect stage of the parasite. The defect in protein glycosylation was rescued by Mn2+ supplementation to the growth medium, underscoring the importance of this transition metal for Golgi glycosylation of proteins.
Highlights
Manganese (Mn2+) is found naturally and is the 12th most abundant element and the 5th most abundant metal
Trypanosoma cruzi is the etiologic agent of Chagas disease, which is endemic from North to South America and the most important cause of heart disease in Latin America
We found that ablation of a Golgi localized cation transporter prevents normal protein glycosylation, host cell invasion, and intracellular replication, and that protein glycosylation can be rescued by Mn2+ but not by Ca2+, Mg2+, or Zn2+, revealing the importance of Mn2+ for host parasite interaction
Summary
Manganese (Mn2+) is found naturally and is the 12th most abundant element and the 5th most abundant metal. Mn2+ is an essential element participating in regulation of metabolism [1], protection from free radical damage [2,3,4] and activation of enzymes [5,6,7]. Enzymes from many different families such as kinases, oxidoreductases, ligases, isomerases, nucleic acid polymerases, sulfotransferases and glycosyl transferases are known to be activated by Mn2+ [10]. Activation of these enzymes requires maintenance of optimal Mn2+ concentration within the cells. Mn2+ homeostasis is achieved by the concerted action of multiple cation transporters that ensure efficient manganese uptake [11,12,13]. Owing to the role of Mn2+ in key cellular processes, investigating the significance of these cation transporters has biological relevance
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