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Sci. Signal., 17 November 2009
Vol. 2, Issue 97, p. ra74
[DOI: 10.1126/scisignal.2000374]

RESEARCH ARTICLES

Trypanosoma cruzi Targets Akt in Host Cells as an Intracellular Antiapoptotic Strategy

Marina V. Chuenkova and Mercio PereiraPerrin*

Parasitology Research Center, Department of Pathology, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111, USA.

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–β. 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.

* To whom correspondence should be addressed. E-mail: maperrin{at}yahoo.com

Citation: M. V. Chuenkova, M. PereiraPerrin, Trypanosoma cruzi Targets Akt in Host Cells as an Intracellular Antiapoptotic Strategy. Sci. Signal. 2, ra74 (2009).

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Multigene Families in Trypanosoma cruzi and Their Role in Infectivity.
L. M. De Pablos and A. Osuna (2012)
Infect. Immun. 80, 2258-2264
   Abstract »    Full Text »    PDF »
Neurotrophin Receptor TrkC Is an Entry Receptor for Trypanosoma cruzi in Neural, Glial, and Epithelial Cells.
C. Weinkauf, R. Salvador, and M. PereiraPerrin (2011)
Infect. Immun. 79, 4081-4087
   Abstract »    Full Text »    PDF »

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