A novel receptor for platelet‐activating factor and lysophosphatidylcholine in Trypanosoma cruzi
| Autor: | 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, Pedro H M Torres |
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| Rok vydání: | 2021 |
| Předmět: |
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 |
| Zdroj: | Molecular Microbiology. 116:890-908 |
| ISSN: | 1365-2958 0950-382X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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