Phosphoproteome dynamics reveal heat-shock protein complexes specific to the Leishmania donovani infectious stage
Open Access
- 19 April 2010
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 107 (18), 8381-8386
- https://doi.org/10.1073/pnas.0914768107
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.Keywords
This publication has 40 references indexed in Scilit:
- The Phosphoproteome of Bloodstream Form Trypanosoma brucei, Causative Agent of African Sleeping SicknessMolecular & Cellular Proteomics, 2009
- Methylene tetrahydrofolate dehydrogenase/cyclohydrolase and the synthesis of 10‐CHO‐THF are essential in Leishmania majorMolecular Microbiology, 2009
- A quantitative atlas of mitotic phosphorylationProceedings of the National Academy of Sciences of the United States of America, 2008
- The Hsp90 Chaperone Machinery Regulates Signaling by Modulating Ligand Binding CleftsPublished by Elsevier BV ,2008
- Novel subsets of the Arabidopsis plasmalemma phosphoproteome identify phosphorylation sites in secondary active transportersBiochemical and Biophysical Research Communications, 2007
- The Genome of the Kinetoplastid Parasite, Leishmania majorScience, 2005
- Gapped BLAST and PSI-BLAST: a new generation of protein database search programsNucleic Acids Research, 1997
- The Role of pH and Temperature in the Development of Leishmania ParasitesAnnual Review of Microbiology, 1994
- Estimation of population at risk of infection and number of cases of LeishmaniasisParasitology Today, 1992
- Leishmanial differentiation : Induction of heat shock proteinsBiochemical and Biophysical Research Communications, 1984