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Rab11 Regulates Trafficking of -sialidase to the Plasma Membrane through the Contractile Vacuole Complex of


Several free-living protozoa possess a contractile vacuole complex (CVC) that protects them from the hyposmotic environments where they live. Interestingly, the intracellular parasite Trypanosoma cruzi, the etiologic agent of Chagas disease, has conserved a CVC in all its developmental stages, where it has an osmoregulatory role under both hyposmotic and hyperosmotic conditions. We found here that the CVC of T. cruzi has an additional unconventional role in traffic of glycosylphosphatidylinositol (GPI)-anchored proteins to the plasma membrane of the parasite. A combination of genetic and biochemical approaches revealed the role of TcRab11, a protein localized to the CVC, in traffic of trans-sialidase (TcTS), a GPI-anchored protein important for host cell invasion, but not of other GPI-anchored proteins or integral membrane proteins, to the plasma membrane. Demonstration of the role of TcTS in infection has been previously difficult given the large number of genes encoding for this protein distributed through the genome of the parasite. However, by constructing dominant negative TcRab11 we were able to prevent traffic of TcTS to the plasma membrane and demonstrate its role in host invasion.


Vyšlo v časopise: Rab11 Regulates Trafficking of -sialidase to the Plasma Membrane through the Contractile Vacuole Complex of. PLoS Pathog 10(6): e32767. doi:10.1371/journal.ppat.1004224
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004224

Souhrn

Several free-living protozoa possess a contractile vacuole complex (CVC) that protects them from the hyposmotic environments where they live. Interestingly, the intracellular parasite Trypanosoma cruzi, the etiologic agent of Chagas disease, has conserved a CVC in all its developmental stages, where it has an osmoregulatory role under both hyposmotic and hyperosmotic conditions. We found here that the CVC of T. cruzi has an additional unconventional role in traffic of glycosylphosphatidylinositol (GPI)-anchored proteins to the plasma membrane of the parasite. A combination of genetic and biochemical approaches revealed the role of TcRab11, a protein localized to the CVC, in traffic of trans-sialidase (TcTS), a GPI-anchored protein important for host cell invasion, but not of other GPI-anchored proteins or integral membrane proteins, to the plasma membrane. Demonstration of the role of TcTS in infection has been previously difficult given the large number of genes encoding for this protein distributed through the genome of the parasite. However, by constructing dominant negative TcRab11 we were able to prevent traffic of TcTS to the plasma membrane and demonstrate its role in host invasion.


Zdroje

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