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?-Arrestin-Dependent Dopaminergic Regulation of Calcium Channel Activity in the Axon Initial Segment.


ABSTRACT: G-protein-coupled receptors (GPCRs) initiate a variety of signaling cascades, depending on effector coupling. ?-arrestins, which were initially characterized by their ability to "arrest" GPCR signaling by uncoupling receptor and G protein, have recently emerged as important signaling effectors for GPCRs. ?-arrestins engage signaling pathways that are distinct from those mediated by G protein. As such, arrestin-dependent signaling can play a unique role in regulating cell function, but whether neuromodulatory GPCRs utilize ?-arrestin-dependent signaling to regulate neuronal excitability remains unclear. Here, we find that D3 dopamine receptors (D3R) regulate axon initial segment (AIS) excitability through ?-arrestin-dependent signaling, modifying CaV3 voltage dependence to suppress high-frequency action potential generation. This non-canonical D3R signaling thereby gates AIS excitability via pathways distinct from classical GPCR signaling pathways.

SUBMITTER: Yang S 

PROVIDER: S-EPMC5074334 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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β-Arrestin-Dependent Dopaminergic Regulation of Calcium Channel Activity in the Axon Initial Segment.

Yang Sungchil S   Ben-Shalom Roy R   Ahn Misol M   Liptak Alayna T AT   van Rijn Richard M RM   Whistler Jennifer L JL   Bender Kevin J KJ  

Cell reports 20160721 6


G-protein-coupled receptors (GPCRs) initiate a variety of signaling cascades, depending on effector coupling. β-arrestins, which were initially characterized by their ability to "arrest" GPCR signaling by uncoupling receptor and G protein, have recently emerged as important signaling effectors for GPCRs. β-arrestins engage signaling pathways that are distinct from those mediated by G protein. As such, arrestin-dependent signaling can play a unique role in regulating cell function, but whether ne  ...[more]

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2024-01-02 | PXD045921 | Pride