Importance of a N-terminal aspartate in the internalization of the neuropeptide Y Y2 receptor

With human neuropeptide Y Y(2) receptor expressed in the Chinese hamster ovary (CHO) cells, the Asp(35)Ala mutation, and especially the change of Pro(34)Asp(35) to Ala(34)Ala(35), decrease the compartmentalization and strongly accelerate internalization of the receptor. These changes are not associated with alterations in agonist affinity, G-protein interaction, dimerization, or level of expression of the mutated receptors relative to the wildtype receptor. The proline-flanked aspartate in the N-terminal extracellular segment of the neuropeptide Y Y(2) receptor thus apparently has a large role in anchoring and compartmentalization of the receptor. However, the Pro(34)Ala mutation does not significantly affect the embedding and cycling of the receptor.