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

Sungchil Yang, Roy Ben-Shalom, Misol Ahn, Alayna T. Liptak, Richard M. van Rijn, Jennifer Whistler, Kevin J. Bender

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

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 neuromodulatory GPCRs utilize β-arrestin-dependent signaling to regulate neuronal excitability remains unclear. Here, we find that D3 dopamine receptors (D3R) regulate axon initial segment (AIS) excitability through β-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.

Original languageEnglish (US)
Pages (from-to)1518-1526
Number of pages9
JournalCell Reports
Volume16
Issue number6
DOIs
StatePublished - Aug 9 2016
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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