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Modulation of the Surface Proteome through Multiple Ubiquitylation Pathways in African Trypanosomes


The mechanisms by which pathogens interact with their environment are of major importance, both for fulfilling the basic needs of the parasite and understanding immune evasion. For African trypanosomes, the surface is dominated by the variant surface glycoprotein (VSG), but recent data has demonstrated an important role for ubiquitylation in mediating turnover of invariant surface glycoproteins (ISGs) and maintaining ISG copy number independent of VSG. Further, ISG expression is required for suramin-sensitivity. Here we describe mechanisms mediating ISG turnover, uncovered using a screen for genes involved in sensitivity to suramin. These involve multiple aspects of the ubiquitylation machinery, and connect ISG turnover with additional surface proteins. Our data provide a first insight into the complexity of regulation of the ISG family, identifying further aspects to the control of a drug-sensitivity pathway in trypanosomes, and offering insights into metabolism of the parasite surface proteome.


Vyšlo v časopise: Modulation of the Surface Proteome through Multiple Ubiquitylation Pathways in African Trypanosomes. PLoS Pathog 11(10): e32767. doi:10.1371/journal.ppat.1005236
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005236

Souhrn

The mechanisms by which pathogens interact with their environment are of major importance, both for fulfilling the basic needs of the parasite and understanding immune evasion. For African trypanosomes, the surface is dominated by the variant surface glycoprotein (VSG), but recent data has demonstrated an important role for ubiquitylation in mediating turnover of invariant surface glycoproteins (ISGs) and maintaining ISG copy number independent of VSG. Further, ISG expression is required for suramin-sensitivity. Here we describe mechanisms mediating ISG turnover, uncovered using a screen for genes involved in sensitivity to suramin. These involve multiple aspects of the ubiquitylation machinery, and connect ISG turnover with additional surface proteins. Our data provide a first insight into the complexity of regulation of the ISG family, identifying further aspects to the control of a drug-sensitivity pathway in trypanosomes, and offering insights into metabolism of the parasite surface proteome.


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