> Details

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

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

Reference
management

Bookmarks

Remove from
bookmarks

Share this on Whatsapp

Close

Bookmarks



You can manage bookmarks using lists, please log in to your user account for this.
  • Media type: E-Article
  • Title: Phosphoproteome dynamics reveal heat-shock protein complexes specific to the Leishmania donovani infectious stage
  • Contributor: Morales, Miguel A.; Watanabe, Reiko; Dacher, Mariko; Chafey, Philippe; Osorio y Fortéa, José; Scott, David A.; Beverley, Stephen M.; Ommen, Gabi; Clos, Joachim; Hem, Sonia; Lenormand, Pascal; Rousselle, Jean-Claude; Namane, Abdelkader; Späth, Gerald F.
  • imprint: Proceedings of the National Academy of Sciences, 2010
  • Published in: Proceedings of the National Academy of Sciences
  • Language: English
  • DOI: 10.1073/pnas.0914768107
  • ISSN: 0027-8424; 1091-6490
  • Keywords: Multidisciplinary
  • Origination:
  • Footnote:
  • Description: <jats:p> <jats:italic>Leishmania</jats:italic> 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 <jats:italic>Leishmania</jats:italic> HSPs. Here we used a gel-based quantitative approach to assess the <jats:italic>Leishmania donovani</jats:italic> 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 <jats:italic> sti1 <jats:sup>−/−</jats:sup> </jats:italic> null mutant parasites revealed two phosphoserine residues essential for parasite viability. Phosphorylation of the major <jats:italic>Leishmania</jats:italic> chaperones at the pathogenic stage suggests that these proteins may be promising drug targets via inhibition of their respective protein kinases. </jats:p>
  • Access State: Open Access