Phosphoproteome dynamics reveal heat-shock protein complexes specific to the Leishmania donovani infectious stage

Miguel A. Morales, Reiko Watanabe, Mariko Dacher, Philippe Chafey, José Osorio Y Fortéa, David A. Scott, Stephen M. Beverley, Gabi Ommen, Joachim Clos, Sonia Hem, Pascal Lenormand, Jean Claude Rousselle, Abdelkader Namane, Gerald F. Späth

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Abstract

Leishmania is exposed to a sudden increase in environmental temperature during the infectious cycle that triggers stage differentiation and adapts the parasite phenotype to intracellular survival in the mammalian host. The absence of classical promoter-dependent mechanisms of gene regulation and constitutive expression of most of the heat-shock proteins (HSPs) in these human pathogens raise important unresolved questions as to regulation of the heat-shock response and stage-specific functions of Leishmania HSPs. Here we used a gel-based quantitative approach to assess the Leishmania donovani phosphoproteome and revealed that 38% of the proteins showed significant stage-specific differences, with a strong focus of amastigote-specific phosphoproteins on chaperone function. We identified STI1/HOP-containing chaperone complexes that interact with ribosomal client proteins in an amastigote-specific manner. Genetic analysis of STI1/HOP phosphorylation sites in conditional sti1-/- null mutant parasites revealed two phosphoserine residues essential for parasite viability. Phosphorylation of the major Leishmania chaperones at the pathogenic stage suggests that these proteins may be promising drug targets via inhibition of their respective protein kinases.

Original languageEnglish
Pages (from-to)8381-8386
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number18
DOIs
Publication statusPublished - 2010 May 4
Externally publishedYes

Keywords

  • Signaling
  • Stress response

ASJC Scopus subject areas

  • General

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  • Cite this

    Morales, M. A., Watanabe, R., Dacher, M., Chafey, P., Osorio Y Fortéa, J., Scott, D. A., Beverley, S. M., Ommen, G., Clos, J., Hem, S., Lenormand, P., Rousselle, J. C., Namane, A., & Späth, G. F. (2010). Phosphoproteome dynamics reveal heat-shock protein complexes specific to the Leishmania donovani infectious stage. Proceedings of the National Academy of Sciences of the United States of America, 107(18), 8381-8386. https://doi.org/10.1073/pnas.0914768107