Internalization of the TXA2 Receptor α and β Isoforms ROLE OF THE DIFFERENTIALLY SPLICED COOH TERMINUS IN AGONIST-PROMOTED RECEPTOR INTERNALIZATION

摘要: Thromboxane A2(TXA2) potently stimulates platelet aggregation and smooth muscle constriction is thought to play a role in myocardial infarction, atherosclerosis, bronchial asthma. The TXA2receptor (TXA2R) member of the G protein-coupled receptor family found as two alternatively spliced isoforms, α (343 residues) β (407 residues), which share first 328 residues. In present report, we demonstrate by enzyme-linked immunosorbent assay immunofluorescence microscopy that TXA2Rβ, but not TXA2Rα, undergoes agonist-induced internalization when expressed HEK293 cells well several other cell types. Various dominant negative mutants were used TXA2Rβ dynamin-, GRK-, arrestin-dependent cells, suggesting involvement phosphorylation clathrin-coated pits this process. Interestingly, agonist-stimulated both mutant truncated after residue 328, can be promoted overexpression arrestin-3, identifying C-tails receptors necessary arrestin-3 interaction. Simultaneous mutation dileucine motifs C-tail did affect agonist-promoted internalization. Analysis various deletion revealed region between residues 355 366 essential for These data alternative splicing TXA2R plays critical regulating arrestin binding subsequent