A global S-palmitoylation map of Trypanosoma cruzi identifies ABCA10 as a key component of a redundant heme-acquisition system
En palabras de los autores
Survival and transmission of the human pathogen Trypanosoma cruzi depend on dynamic remodeling of its membrane proteome, yet the post-translational networks governing this plasticity remain obscure. Using metabolic labeling and quantitative mass spectrometry, we present a comprehensive map of the T. cruzi S-palmitoylome: a high-confidence atlas of 254 proteins enriched for signaling factors, cytoskeletal regulators, and membrane transporters. Functional screening with our aptazyme-based SHARK knockdown system identifies ABCA10, an uncharacterized ABC transporter central to heme homeostasis. Depletion of ABCA10 triggers a compensatory surge in cytostome-mediated endocytosis, rendering this normally dispensable process conditionally essential. ABCA10 expression is itself heme-regulated and upon heme starvation it redistributes from the flagellar pocket to pre-lysosomal reservosomes. We further show that endocytosis is directly tuned by extracellular heme, placing the entire uptake apparatus, not only ABCA10, under heme-responsive control. Together, these findings reveal a redundant heme-scavenging strategy and expose a druggable vulnerability in a neglected pathogen. The Chagas disease parasite, T. cruzi, cannot make heme, and so must steal it to survive. Researchers mapping its fatty-acid-tagged proteins identified ABCA10, an ABC transporter at the core of this heme-scavenging system and a promising new drug target.
Apareció: sábado, 26 de septiembre. Nature Communications. Revista con revisión por pares.