Towards improved receptor targeting: anterograde transport, internalization and postendocytic trafficking of neuropeptide Y receptors

Biol Chem. 2013 Aug;394(8):921-36. doi: 10.1515/hsz-2013-0123.


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 receptor-ligand 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Endocytosis
  • Humans
  • Molecular Sequence Data
  • Protein Transport
  • Proteolysis
  • Receptors, Neuropeptide Y / analysis*
  • Receptors, Neuropeptide Y / metabolism*


  • Receptors, Neuropeptide Y