1. A novel receptor for platelet‐activating factor and lysophosphatidylcholine in Trypanosoma cruzi
- Author
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Stenio P Fragoso, Danielle P. Vieira, Felipe S. Coelho, Isabel C F Moreira, Adriana Cabanelas, Angela H. Lopes, Inês C. Gonçalves, Erica S. Martins-Duarte, Pedro G. Pascutti, Mauricio M. Oliveira, and Pedro H M Torres
- Subjects
Protein Conformation ,Trypanosoma cruzi ,Cellular differentiation ,Protozoan Proteins ,Biology ,Microbiology ,Host-Parasite Interactions ,Gene Knockout Techniques ,Mice ,chemistry.chemical_compound ,parasitic diseases ,Animals ,Humans ,Chagas Disease ,Amino Acid Sequence ,Platelet Activating Factor ,Receptor ,Molecular Biology ,Phylogeny ,Gene knockout ,Platelet-activating factor ,Macrophages ,Lysophosphatidylcholines ,Cell Differentiation ,Lipid signaling ,biology.organism_classification ,Molecular biology ,In vitro ,Molecular Docking Simulation ,Lysophosphatidylcholine ,chemistry ,lipids (amino acids, peptides, and proteins) ,Receptors, Adiponectin ,Receptors, Progesterone - Abstract
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 (WT) 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.
- Published
- 2021