title: Trypanosoma cruzi targets Akt in host cells as an intracellular antiapoptotic strategy.
abstract: The parasite Trypanosoma cruzi, which causes Chagas' disease, differentiates in the cytosol of its host cell and then replicates and spreads infection, processes that require the long-term survival of the infected cells. Here, we show that in the cytosol, parasite-derived neurotrophic factor (PDNF), a trans-sialidase that is located on the surface of T. cruzi, is both a substrate and an activator of the serine-threonine kinase Akt, an antiapoptotic molecule. PDNF increases the expression of the gene that encodes Akt while suppressing the transcription of genes that encode proapoptotic factors. Consequently, PDNF elicits a sustained functional response that protects host cells from apoptosis induced by oxidative stress and the proinflammatory cytokines tumor necrosis factor-alpha and transforming growth factor-beta. Given that PDNF also activates Akt by binding to the neurotrophic surface receptor TrkA, we propose that this protein activates survival signaling both at the cell surface, by acting as a receptor-binding ligand, and inside cells, by acting as a scaffolding adaptor protein downstream of the receptor.
authors.affiliation: Parasitology Research Center, Department of Pathology, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111, USA.
authors.forename: Marina V
authors.initials: MV
authors.lastname: Chuenkova
authors.forename: Mercio
authors.initials: M
authors.lastname: PereiraPerrin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D015153:Blotting, Western; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006790:Host-Parasite Interactions; D006801:Humans; D047468:Immunoprecipitation; D042541:Intracellular Space / Q000378:metabolism / Q000469:parasitology; D009439:Neuraminidase / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012583:Schwann Cells / Q000166:cytology / Q000378:metabolism / Q000469:parasitology; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000201:enzymology / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D006023:Glycoproteins; D015800:Protozoan Proteins; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D051057:Proto-Oncogene Proteins c-akt; C069715:trans-sialidase; D009439:Neuraminidase