Different mode of arrestin-3 binding at the human Y1 and Y2 receptor.

摘要: GPCR internalization, which is induced by arrestin recruitment, an important mechanism for the regulation of signaling and receptor quantity at cell surface. In this study, differences in arrestin-3 (arr-3) recruitment to neuropeptide Y1 Y2 were identified. These receptors play essential role feeding, energy homeostasis cancer. The Y1R displays high affinity arr-3, induces rapid internalization arrestin/receptor complex. contrast, Y2R has a lower arr-3. Internalization binding, but arr-3 released from remains membrane while internalizes. Moreover, deletion finger loop region reduces its agonist-dependent significantly, not suggesting different binding conformations. For first time, formation supercomplex consisting Y receptor, Gα0 protein was studied BRET-assay. We demonstrated that able bind as well simultaneously internalizes supercomplex. no observed. By substituting C-terminus or specific residues within intracellular 1 2 receptors, can be switched. Thus, we shed light on spatio-temporal distribution response versus activation identified molecular determinants.