Coassembly and coupling of SK2 channels and mGlu5 receptors

Gloria García-Negredo; David Soto; Javier Llorente; Xavier Morató; Koen M.O. Galenkamp; Maricel Gómez-Soler; Víctor Fernández-Dueñas; Masahiko Watanabe; John P. Adelman; Ryuichi Shigemoto; Yugo Fukazawa; Rafael Luján; Francisco Ciruela

doi:10.1523/JNEUROSCI.2038-14.2014

Coassembly and coupling of SK2 channels and mGlu₅ receptors

Gloria García-Negredo, David Soto, Javier Llorente, Xavier Morató, Koen M.O. Galenkamp, Maricel Gómez-Soler, Víctor Fernández-Dueñas, Masahiko Watanabe, John P. Adelman, Ryuichi Shigemoto, Yugo Fukazawa, Rafael Luján, Francisco Ciruela

Vollum Institute

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

Abstract

Group I metabotropic glutamate (mGlu) receptors regulate hippocampal CA1 pyramidal neuron excitability via Ca²⁺ wave-dependent activation of small-conductance Ca²⁺ -activated K⁺ (SK) channels. Here, we show that mGlu₅ receptors and SK2 channels coassemble in heterologous coexpression systems and in rat brain. Further, in cotransfected cells or rat primary hippocampal neurons, mGlu₅ receptor stimulation activated apamin-sensitive SK2-mediated K⁺ currents. In addition, coexpression of mGlu₅ receptors and SK2 channels promoted plasma membrane targeting of both proteins and correlated with increased mGlu₅ receptor function that was unexpectedly blocked by apamin. These results demonstrate a reciprocal functional interaction between mGlu₅ receptors and SK2 channels that reflects their molecular coassembly.

Original language	English (US)
Pages (from-to)	14793-14802
Number of pages	10
Journal	Journal of Neuroscience
Volume	34
Issue number	44
DOIs	https://doi.org/10.1523/JNEUROSCI.2038-14.2014
State	Published - Oct 29 2014

Keywords

Apamin
Electron microscopy
Oligomerization
SK2 channel
mGlu receptor

ASJC Scopus subject areas

General Neuroscience

Access to Document

10.1523/JNEUROSCI.2038-14.2014

Cite this

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title = "Coassembly and coupling of SK2 channels and mGlu5 receptors",

abstract = "Group I metabotropic glutamate (mGlu) receptors regulate hippocampal CA1 pyramidal neuron excitability via Ca2+ wave-dependent activation of small-conductance Ca2+ -activated K+ (SK) channels. Here, we show that mGlu5 receptors and SK2 channels coassemble in heterologous coexpression systems and in rat brain. Further, in cotransfected cells or rat primary hippocampal neurons, mGlu5 receptor stimulation activated apamin-sensitive SK2-mediated K+ currents. In addition, coexpression of mGlu5 receptors and SK2 channels promoted plasma membrane targeting of both proteins and correlated with increased mGlu5 receptor function that was unexpectedly blocked by apamin. These results demonstrate a reciprocal functional interaction between mGlu5 receptors and SK2 channels that reflects their molecular coassembly.",

keywords = "Apamin, Electron microscopy, Oligomerization, SK2 channel, mGlu receptor",

author = "Gloria Garc{\'i}a-Negredo and David Soto and Javier Llorente and Xavier Morat{\'o} and Galenkamp, {Koen M.O.} and Maricel G{\'o}mez-Soler and V{\'i}ctor Fern{\'a}ndez-Due{\~n}as and Masahiko Watanabe and Adelman, {John P.} and Ryuichi Shigemoto and Yugo Fukazawa and Rafael Luj{\'a}n and Francisco Ciruela",

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T1 - Coassembly and coupling of SK2 channels and mGlu5 receptors

AU - García-Negredo, Gloria

AU - Soto, David

AU - Llorente, Javier

AU - Morató, Xavier

AU - Galenkamp, Koen M.O.

AU - Gómez-Soler, Maricel

AU - Fernández-Dueñas, Víctor

AU - Watanabe, Masahiko

AU - Adelman, John P.

AU - Shigemoto, Ryuichi

AU - Fukazawa, Yugo

AU - Luján, Rafael

AU - Ciruela, Francisco

PY - 2014/10/29

Y1 - 2014/10/29

N2 - Group I metabotropic glutamate (mGlu) receptors regulate hippocampal CA1 pyramidal neuron excitability via Ca2+ wave-dependent activation of small-conductance Ca2+ -activated K+ (SK) channels. Here, we show that mGlu5 receptors and SK2 channels coassemble in heterologous coexpression systems and in rat brain. Further, in cotransfected cells or rat primary hippocampal neurons, mGlu5 receptor stimulation activated apamin-sensitive SK2-mediated K+ currents. In addition, coexpression of mGlu5 receptors and SK2 channels promoted plasma membrane targeting of both proteins and correlated with increased mGlu5 receptor function that was unexpectedly blocked by apamin. These results demonstrate a reciprocal functional interaction between mGlu5 receptors and SK2 channels that reflects their molecular coassembly.

AB - Group I metabotropic glutamate (mGlu) receptors regulate hippocampal CA1 pyramidal neuron excitability via Ca2+ wave-dependent activation of small-conductance Ca2+ -activated K+ (SK) channels. Here, we show that mGlu5 receptors and SK2 channels coassemble in heterologous coexpression systems and in rat brain. Further, in cotransfected cells or rat primary hippocampal neurons, mGlu5 receptor stimulation activated apamin-sensitive SK2-mediated K+ currents. In addition, coexpression of mGlu5 receptors and SK2 channels promoted plasma membrane targeting of both proteins and correlated with increased mGlu5 receptor function that was unexpectedly blocked by apamin. These results demonstrate a reciprocal functional interaction between mGlu5 receptors and SK2 channels that reflects their molecular coassembly.

KW - Apamin

KW - Electron microscopy

KW - Oligomerization

KW - SK2 channel

KW - mGlu receptor

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