Internalization studies of chimeric neuropeptide Y receptors Y1 and Y2 suggest complex interactions between cytoplasmic domains

► The internalization of the neuropeptide Y Y2 receptor is concentration dependent. ► At physiological concentrations Y2 has lower internalization than Y1. ► Low internalization is conserved within the Y2-subfamily receptors. ► No conserved internalization motifs indicated within Y2-subfamily receptors. ► Interchange of intracellular segments between subtypes gives novel phenotypes.