A novel receptor for platelet-activating factor and lysophosphatidylcholine in Trypanosoma cruzi.
Felipe S CoelhoMauricio M OliveiraDanielle P VieiraPedro H M TorresIsabel C F MoreiraErica S Martins-DuarteInês C GonçalvesAdriana CabanelasPedro G PascuttiStenio P FragosoAngela H LopesPublished in: Molecular microbiology (2021)
The lipid mediators, platelet-activating factor (PAF) and lysophosphatidylcholine (LPC), play relevant pathophysiological roles in Trypanosoma cruzi infection. Several species of LPC, including C18:1 LPC, which mimics the effects of PAF, are synthesized by T. cruzi. The present study identified a receptor in T. cruzi, which was predicted to bind to PAF, and found it to be homologous to members of the progestin and adiponectin family of receptors (PAQRs). We constructed a three-dimensional model of the T. cruzi PAQR (TcPAQR) and performed molecular docking to predict the interactions of the TcPAQR model with C16:0 PAF and C18:1 LPC. We knocked out T. cruzi PAQR (TcPAQR) gene and confirmed the identity of the expressed protein through immunoblotting and immunofluorescence assays using an anti-human PAQR antibody. Wild-type and knockout (KO) parasites were also used to investigate the in vitro cell differentiation and interactions with peritoneal mouse macrophages; TcPAQR KO parasites were unable to react to C16:0 PAF or C18:1 LPC. Our data are highly suggestive that PAF and LPC act through TcPAQR in T. cruzi, triggering its cellular differentiation and ability to infect macrophages.
Keyphrases
- trypanosoma cruzi
- molecular docking
- wild type
- signaling pathway
- endothelial cells
- molecular dynamics simulations
- metabolic syndrome
- binding protein
- high throughput
- type diabetes
- big data
- genome wide
- dna damage
- electronic health record
- machine learning
- copy number
- small molecule
- insulin resistance
- protein protein
- skeletal muscle
- pluripotent stem cells