Towards improved receptor targeting: Anterograde transport, internalization and postendocytic trafficking of neuropeptide y receptors

Abstract

The neuropeptide Y system is known to be involved in the regulation of many central physiological and pathophysiological processes, such as energy homeostasis, obesity, cancer, mood disorders and epilepsy. Four Y receptor subtypes have been cloned from human tissue (hY1, hY2, hY4 and hY5 ) that form a multiligand/multireceptor system together with their three peptidic agonists (NPY, PYY and PP). Addressing this system for medical application requires on the one hand detailed information about the receptorligand interaction to design subtype-selective compounds. On the other hand comprehensive knowledge about alternative receptor signaling, as well as desensitization, localization and downregulation is crucial to circumvent the development of undesired side-effects and drug resistance. By bringing such knowledge together, highly potent and long-lasting drugs with minimized side-effects can be engineered. Here, current knowledge about Y receptor export, internalization, recycling, and degradation is summarized, with a focus on the human Y receptor subtypes, and is discussed in terms of its impact on therapeutic application.