β-COP Regulates TWIK1/TREK1 Heterodimeric Channel-Mediated Passive Conductance in Astrocytes

Seong Seop Kim; Yeonju Bae; Osung Kwon; Seung Hae Kwon; Jong Bok Seo; Eun Mi Hwang; Jae Yong Park

doi:10.3390/cells11203322

β-COP Regulates TWIK1/TREK1 Heterodimeric Channel-Mediated Passive Conductance in Astrocytes

Seong Seop Kim, Yeonju Bae, Osung Kwon, Seung Hae Kwon, Jong Bok Seo, Eun Mi Hwang, Jae Yong Park

School of Biosystem and Biomedical Science

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

1 Citation (Scopus)

Abstract

Mature astrocytes are characterized by a K⁺ conductance (passive conductance) that changes with a constant slope with voltage, which is involved in K⁺ homeostasis in the brain. Recently, we reported that the tandem of pore domains in a weak inward rectifying K⁺ channel (TWIK1 or KCNK1) and TWIK-related K⁺ channel 1 (TREK1 or KCNK2) form heterodimeric channels that mediate passive conductance in astrocytes. However, little is known about the binding proteins that regulate the function of the TWIK1/TREK1 heterodimeric channels. Here, we found that β-coat protein (COP) regulated the surface expression and activity of the TWIK1/TREK1 heterodimeric channels in astrocytes. β-COP binds directly to TREK1 but not TWIK1 in a heterologous expression system. However, β-COP also interacts with the TWIK1/TREK1 heterodimeric channel in a TREK1 dependent manner and enhances the surface expression of the heterodimeric channel in astrocytes. Consequently, it regulates TWIK1/TREK1 heterodimeric channel-mediated passive conductance in astrocytes in the mouse brain. Taken together, these results suggest that β-COP is a potential regulator of astrocytic passive conductance in the brain.

Original language	English
Article number	3322
Journal	Cells
Volume	11
Issue number	20
DOIs	https://doi.org/10.3390/cells11203322
Publication status	Published - 2022 Oct

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation (NRF) of Korea (NRF-2017R1A2B3012502 and NRF-2016M3C7A1904149).

Publisher Copyright:
© 2022 by the authors.

Keywords

TREK1
TWIK1
astrocytes
passive conductance
protein–protein interaction
β-COP

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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10.3390/cells11203322

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title = "β-COP Regulates TWIK1/TREK1 Heterodimeric Channel-Mediated Passive Conductance in Astrocytes",

abstract = "Mature astrocytes are characterized by a K+ conductance (passive conductance) that changes with a constant slope with voltage, which is involved in K+ homeostasis in the brain. Recently, we reported that the tandem of pore domains in a weak inward rectifying K+ channel (TWIK1 or KCNK1) and TWIK-related K+ channel 1 (TREK1 or KCNK2) form heterodimeric channels that mediate passive conductance in astrocytes. However, little is known about the binding proteins that regulate the function of the TWIK1/TREK1 heterodimeric channels. Here, we found that β-coat protein (COP) regulated the surface expression and activity of the TWIK1/TREK1 heterodimeric channels in astrocytes. β-COP binds directly to TREK1 but not TWIK1 in a heterologous expression system. However, β-COP also interacts with the TWIK1/TREK1 heterodimeric channel in a TREK1 dependent manner and enhances the surface expression of the heterodimeric channel in astrocytes. Consequently, it regulates TWIK1/TREK1 heterodimeric channel-mediated passive conductance in astrocytes in the mouse brain. Taken together, these results suggest that β-COP is a potential regulator of astrocytic passive conductance in the brain.",

keywords = "TREK1, TWIK1, astrocytes, passive conductance, protein–protein interaction, β-COP",

author = "Kim, {Seong Seop} and Yeonju Bae and Osung Kwon and Kwon, {Seung Hae} and Seo, {Jong Bok} and Hwang, {Eun Mi} and Park, {Jae Yong}",

note = "Funding Information: This work was supported by the National Research Foundation (NRF) of Korea (NRF-2017R1A2B3012502 and NRF-2016M3C7A1904149). Publisher Copyright: {\textcopyright} 2022 by the authors.",

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AU - Kim, Seong Seop

AU - Bae, Yeonju

AU - Kwon, Osung

AU - Kwon, Seung Hae

AU - Seo, Jong Bok

AU - Hwang, Eun Mi

AU - Park, Jae Yong

PY - 2022/10

Y1 - 2022/10

N2 - Mature astrocytes are characterized by a K+ conductance (passive conductance) that changes with a constant slope with voltage, which is involved in K+ homeostasis in the brain. Recently, we reported that the tandem of pore domains in a weak inward rectifying K+ channel (TWIK1 or KCNK1) and TWIK-related K+ channel 1 (TREK1 or KCNK2) form heterodimeric channels that mediate passive conductance in astrocytes. However, little is known about the binding proteins that regulate the function of the TWIK1/TREK1 heterodimeric channels. Here, we found that β-coat protein (COP) regulated the surface expression and activity of the TWIK1/TREK1 heterodimeric channels in astrocytes. β-COP binds directly to TREK1 but not TWIK1 in a heterologous expression system. However, β-COP also interacts with the TWIK1/TREK1 heterodimeric channel in a TREK1 dependent manner and enhances the surface expression of the heterodimeric channel in astrocytes. Consequently, it regulates TWIK1/TREK1 heterodimeric channel-mediated passive conductance in astrocytes in the mouse brain. Taken together, these results suggest that β-COP is a potential regulator of astrocytic passive conductance in the brain.

AB - Mature astrocytes are characterized by a K+ conductance (passive conductance) that changes with a constant slope with voltage, which is involved in K+ homeostasis in the brain. Recently, we reported that the tandem of pore domains in a weak inward rectifying K+ channel (TWIK1 or KCNK1) and TWIK-related K+ channel 1 (TREK1 or KCNK2) form heterodimeric channels that mediate passive conductance in astrocytes. However, little is known about the binding proteins that regulate the function of the TWIK1/TREK1 heterodimeric channels. Here, we found that β-coat protein (COP) regulated the surface expression and activity of the TWIK1/TREK1 heterodimeric channels in astrocytes. β-COP binds directly to TREK1 but not TWIK1 in a heterologous expression system. However, β-COP also interacts with the TWIK1/TREK1 heterodimeric channel in a TREK1 dependent manner and enhances the surface expression of the heterodimeric channel in astrocytes. Consequently, it regulates TWIK1/TREK1 heterodimeric channel-mediated passive conductance in astrocytes in the mouse brain. Taken together, these results suggest that β-COP is a potential regulator of astrocytic passive conductance in the brain.

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β-COP Regulates TWIK1/TREK1 Heterodimeric Channel-Mediated Passive Conductance in Astrocytes

Abstract

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