Phosphoproteome dynamics reveal heat-shock protein complexes specific to the Leishmania donovani infectious stage. - Archive ouverte HAL Access content directly
Journal Articles Proceedings of the National Academy of Sciences of the United States of America Year : 2010

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

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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.

Dates and versions

pasteur-00476914 , version 1 (27-04-2010)

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Miguel A Morales, Reiko Watanabe, Mariko Dacher, Philippe Chafey, José Osorio y Fortéa, et al.. 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, 2010, epub ahead of print. ⟨10.1073/pnas.0914768107⟩. ⟨pasteur-00476914⟩
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