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 language | English (US) |
|---|---|
| Pages (from-to) | 1518-1526 |
| Number of pages | 9 |
| Journal | Cell Reports |
| Volume | 16 |
| Issue number | 6 |
| DOIs | |
| State | Published - Aug 9 2016 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
Cite this
β-Arrestin-Dependent Dopaminergic Regulation of Calcium Channel Activity in the Axon Initial Segment. / Yang, Sungchil; Ben-Shalom, Roy; Ahn, Misol; Liptak, Alayna T.; van Rijn, Richard M.; Whistler, Jennifer; Bender, Kevin J.
In: Cell Reports, Vol. 16, No. 6, 09.08.2016, p. 1518-1526.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - β-Arrestin-Dependent Dopaminergic Regulation of Calcium Channel Activity in the Axon Initial Segment
AU - Yang, Sungchil
AU - Ben-Shalom, Roy
AU - Ahn, Misol
AU - Liptak, Alayna T.
AU - van Rijn, Richard M.
AU - Whistler, Jennifer
AU - Bender, Kevin J.
PY - 2016/8/9
Y1 - 2016/8/9
N2 - 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.
AB - 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.
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U2 - 10.1016/j.celrep.2016.06.098
DO - 10.1016/j.celrep.2016.06.098
M3 - Article
VL - 16
SP - 1518
EP - 1526
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 6
ER -