title: Phosphoproteome dynamics reveal heat-shock protein complexes specific to the Leishmania donovani infectious stage.
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.
authors.affiliation: Institut Pasteur, G5 Virulence Parasitaire, 75015 Paris, France.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Morales
authors.forename: Reiko
authors.initials: R
authors.lastname: Watanabe
authors.forename: Mariko
authors.initials: M
authors.lastname: Dacher
authors.forename: Philippe
authors.initials: P
authors.lastname: Chafey
authors.forename: José
authors.initials: J
authors.lastname: Osorio y Fortéa
authors.forename: David A
authors.initials: DA
authors.lastname: Scott
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Beverley
authors.forename: Gabi
authors.initials: G
authors.lastname: Ommen
authors.forename: Joachim
authors.initials: J
authors.lastname: Clos
authors.forename: Sonia
authors.initials: S
authors.lastname: Hem
authors.forename: Pascal
authors.initials: P
authors.lastname: Lenormand
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Rousselle
authors.forename: Abdelkader
authors.initials: A
authors.lastname: Namane
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Späth
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D007893:Leishmania donovani / Q000254:growth & development / Q000378:metabolism*; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D020543:Proteome / Q000737:chemistry / Q000378:metabolism*; D015800:Protozoan Proteins / Q000737:chemistry / Q000378:metabolism*; D016415:Sequence Alignment
chemical_list: D006360:Heat-Shock Proteins; D010750:Phosphoproteins; D020543:Proteome; D015800:Protozoan Proteins
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