A disulphide-linked heterodimer of TWIK-1 and TREK-1 mediates passive conductance in astrocytes

Eun Mi Hwang; Eunju Kim; Oleg Yarishkin; Dong Ho Woo; Kyung Seok Han; Nammi Park; Yeonju Bae; Junsung Woo; Donggyu Kim; Myeongki Park; C. Justin Lee; Jae Yong Park

doi:10.1038/ncomms4227

A disulphide-linked heterodimer of TWIK-1 and TREK-1 mediates passive conductance in astrocytes

Eun Mi Hwang, Eunju Kim, Oleg Yarishkin, Dong Ho Woo, Kyung Seok Han, Nammi Park, Yeonju Bae, Junsung Woo, Donggyu Kim, Myeongki Park, C. Justin Lee, Jae Yong Park

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Abstract

TWIK-1 is a member of the two-pore domain K + (K2P) channel family that plays an essential part in the regulation of resting membrane potential and cellular excitability. The physiological role of TWIK-1 has remained enigmatic because functional expression of TWIK-1 channels is elusive. Here we report that native TWIK-1 forms a functional channel at the plasma membrane of astrocytes. A search for TWIK-1-binding proteins led to the identification of TREK-1, another member of the K2P family. The TWIK-1/TREK-1 heterodimeric channel is formed via a disulphide bridge between residue C69 in TWIK-1 and C93 in TREK-1. Gene silencing demonstrates that surface expression of TWIK-1 and TREK-1 are interdependent. TWIK-1/TREK-1 heterodimers mediate astrocytic passive conductance and cannabinoid-induced glutamate release from astrocytes. Our study sheds new light on the diversity of K2P channels.

Original language	English
Article number	3227
Journal	Nature communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms4227
Publication status	Published - 2014 Feb 5

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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@article{a7a30dcb1cb24c1c8691d23d05d4f7f6,

title = "A disulphide-linked heterodimer of TWIK-1 and TREK-1 mediates passive conductance in astrocytes",

abstract = "TWIK-1 is a member of the two-pore domain K + (K2P) channel family that plays an essential part in the regulation of resting membrane potential and cellular excitability. The physiological role of TWIK-1 has remained enigmatic because functional expression of TWIK-1 channels is elusive. Here we report that native TWIK-1 forms a functional channel at the plasma membrane of astrocytes. A search for TWIK-1-binding proteins led to the identification of TREK-1, another member of the K2P family. The TWIK-1/TREK-1 heterodimeric channel is formed via a disulphide bridge between residue C69 in TWIK-1 and C93 in TREK-1. Gene silencing demonstrates that surface expression of TWIK-1 and TREK-1 are interdependent. TWIK-1/TREK-1 heterodimers mediate astrocytic passive conductance and cannabinoid-induced glutamate release from astrocytes. Our study sheds new light on the diversity of K2P channels.",

author = "{Mi Hwang}, Eun and Eunju Kim and Oleg Yarishkin and {Ho Woo}, Dong and Han, {Kyung Seok} and Nammi Park and Yeonju Bae and Junsung Woo and Donggyu Kim and Myeongki Park and Lee, {C. Justin} and Park, {Jae Yong}",

note = "Funding Information: This work was supported by the MRC (2005-0049415) and the World Class Institute (WCI 2009-003) programs of the National Research Foundation (NRF) funded by the Korean Ministry of Science, Education and Technology (MEST), and also supported by National Agenda Project (NAP) of the Korea Research Council of Fundamental Science and Technology (NAP-09-04). We thank George Augustine and Eunmi Hur for careful editing of the manuscript.",

year = "2014",

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day = "5",

doi = "10.1038/ncomms4227",

language = "English",

volume = "5",

journal = "Nature Communications",

issn = "2041-1723",

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TY - JOUR

T1 - A disulphide-linked heterodimer of TWIK-1 and TREK-1 mediates passive conductance in astrocytes

AU - Mi Hwang, Eun

AU - Kim, Eunju

AU - Yarishkin, Oleg

AU - Ho Woo, Dong

AU - Han, Kyung Seok

AU - Park, Nammi

AU - Bae, Yeonju

AU - Woo, Junsung

AU - Kim, Donggyu

AU - Park, Myeongki

AU - Lee, C. Justin

AU - Park, Jae Yong

N1 - Funding Information: This work was supported by the MRC (2005-0049415) and the World Class Institute (WCI 2009-003) programs of the National Research Foundation (NRF) funded by the Korean Ministry of Science, Education and Technology (MEST), and also supported by National Agenda Project (NAP) of the Korea Research Council of Fundamental Science and Technology (NAP-09-04). We thank George Augustine and Eunmi Hur for careful editing of the manuscript.

PY - 2014/2/5

Y1 - 2014/2/5

N2 - TWIK-1 is a member of the two-pore domain K + (K2P) channel family that plays an essential part in the regulation of resting membrane potential and cellular excitability. The physiological role of TWIK-1 has remained enigmatic because functional expression of TWIK-1 channels is elusive. Here we report that native TWIK-1 forms a functional channel at the plasma membrane of astrocytes. A search for TWIK-1-binding proteins led to the identification of TREK-1, another member of the K2P family. The TWIK-1/TREK-1 heterodimeric channel is formed via a disulphide bridge between residue C69 in TWIK-1 and C93 in TREK-1. Gene silencing demonstrates that surface expression of TWIK-1 and TREK-1 are interdependent. TWIK-1/TREK-1 heterodimers mediate astrocytic passive conductance and cannabinoid-induced glutamate release from astrocytes. Our study sheds new light on the diversity of K2P channels.

AB - TWIK-1 is a member of the two-pore domain K + (K2P) channel family that plays an essential part in the regulation of resting membrane potential and cellular excitability. The physiological role of TWIK-1 has remained enigmatic because functional expression of TWIK-1 channels is elusive. Here we report that native TWIK-1 forms a functional channel at the plasma membrane of astrocytes. A search for TWIK-1-binding proteins led to the identification of TREK-1, another member of the K2P family. The TWIK-1/TREK-1 heterodimeric channel is formed via a disulphide bridge between residue C69 in TWIK-1 and C93 in TREK-1. Gene silencing demonstrates that surface expression of TWIK-1 and TREK-1 are interdependent. TWIK-1/TREK-1 heterodimers mediate astrocytic passive conductance and cannabinoid-induced glutamate release from astrocytes. Our study sheds new light on the diversity of K2P channels.

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JO - Nature Communications

JF - Nature Communications

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A disulphide-linked heterodimer of TWIK-1 and TREK-1 mediates passive conductance in astrocytes

Abstract

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