Dynamin and Rab5a-dependent Trafficking and Signaling of the Neurokinin 1 Receptor

摘要: Understanding the molecular mechanisms of agonist-induced trafficking G-protein-coupled receptors is important because essential role in signal transduction. We examined GTPases dynamin 1 and Rab5a substance P (SP)-induced signaling neurokinin receptor (NK1R), an mediator pain, depression, inflammation, by studying transfected cells enteric neurons that naturally express NK1R. In unstimulated cells, NK1R colocalized with at plasma membrane, was detected endosomes. SP induced translocation into endosomes containing immediately beneath membrane then a perinuclear location. Expression dominant negative mutants K44E Rab5aS34N inhibited endocytosis 45 32%, respectively. Dynamin caused retention NK1R, whereas also impeded from superficially located to Both strongly resensitization SP-induced Ca2+ mobilization 60 85%, respectively, but had no effect on desensitization. not markedly reduced phosphorylation extracellular regulated kinases 2. Thus, mediates formation both endosomal their superficial Rab5a-dependent for necessary desensitization signaling. Dynamin-dependent required coupling mitogen-activated protein kinase cascade. These processes may regulate nociceptive, depressive, proinflammatory effects SP.