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Trafficking and signaling of G protein-coupled receptors in the nervous system: implications for disease and therapy

Bunnett, N. W. and Cottrell, G. S. ORCID: (2010) Trafficking and signaling of G protein-coupled receptors in the nervous system: implications for disease and therapy. CNS & Neurological Disorders - Drug Targets, 9 (5). pp. 539-556. ISSN 1996-3181

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To link to this item DOI: 10.2174/187152710793361621


G protein-coupled receptors (GPCRs) are expressed throughout the nervous system where they regulate multiple physiological processes, participate in neurological diseases, and are major targets for therapy. Given that many GPCRs respond to neurotransmitters and hormones that are present in the extracellular fluid and which do not readily cross the plasma membrane, receptor trafficking to and from the plasma membrane is a critically important determinant of cellular responsiveness. Moreover, trafficking of GPCRs throughout the endosomal system can initiate signaling events that are mechanistically and functionally distinct from those operating at the plasma membrane. This review discusses recent advances in the relationship between signaling and trafficking of GPCRs in the nervous system. It summarizes how receptor modifications influence trafficking, discusses mechanisms that regulate GPCR trafficking to and from the plasma membrane, reviews the relationship between trafficking and signaling, and considers the implications of GPCR trafficking to drug development.

Item Type:Article
Divisions:No Reading authors. Back catalogue items
ID Code:30255
Uncontrolled Keywords:Alternative Splicing Animals Arrestins/physiology Cell Membrane/metabolism/physiology Drug Delivery Systems/methods Endosomes/metabolism G-Protein-Coupled Receptor Kinases/physiology Heterotrimeric GTP-Binding Proteins/physiology Humans Models, Biological Models, Genetic Nervous System Diseases/*drug therapy/metabolism Peptide Hydrolases/metabolism Protein Transport/*physiology Receptors, G-Protein-Coupled/agonists/antagonists & inhibitors/genetics/*metabolism Signal Transduction/*physiology
Additional Information:Bunnett, Nigel W Cottrell, Graeme S DK39957/DK/NIDDK NIH HHS/ DK43207/DK/NIDDK NIH HHS/ DK57840/DK/NIDDK NIH HHS/ FS/08/017/25027/PHS HHS/ British Heart Foundation/United Kingdom United Arab Emirates CNS Neurol Disord Drug Targets. 2010 Nov;9(5):539-56.
Publisher:Bentham Science

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