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

CNS & Neurological Disorders Drug Targets
Nigel W Bunnett, Graeme S Cottrell

Abstract

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.

Citations

Jul 24, 2012·Proceedings of the National Academy of Sciences of the United States of America·Richard H AnderssonAndres Buonanno
Dec 18, 2012·Periodontology 2000·Binnaz LeblebiciogluAngelo Mariotti
May 23, 2014·The Journal of Biological Chemistry·Achla GuptaLakshmi A Devi
Dec 22, 2017·International Journal of STD & AIDS·Sampurna KakchapatiTarun Poudel
Aug 9, 2020·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·David A Lovejoy, David W Hogg
Aug 4, 2019·Journal of Clinical Medicine·Davide CerviaGiovanni Casini

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