Identification of transthyretin as a novel interacting partner for the δ subunit of GABA A receptors

Li Zhou, Xin Tang, Xinyi Li, Yuting Bai, Joel N. Buxbaum, Gong Chen

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

GABA A receptors (GABA A -Rs) play critical roles in brain development and synchronization of neural network activity. While synaptic GABA A -Rs can exert rapid inhibition, the extrasynaptic GABA A -Rs can tonically inhibit neuronal activity due to constant activation by ambient GABA. The δ subunit-containing GABA A -Rs are expressed abundantly in the cerebellum, hippocampus and thalamus to mediate the major tonic inhibition in the brain. While electrophysiological and pharmacological properties of the δ-GABA A -Rs have been well characterized, the molecular interacting partners of the δ-GABA A -Rs are not clearly defined. Here, using a yeast two-hybrid screening assay, we identified transthyretin (TTR) as a novel regulatory molecule for the δ-GABA A -Rs. Knockdown of TTR in cultured cerebellar granule neurons significantly decreased the δ receptor expression; whereas overexpressing TTR in cortical neurons increased the δ receptor expression. Electrophysiological analysis confirmed that knockdown or overexpression of TTR in cultured neurons resulted in a corresponding decrease or increase of tonic currents. Furthermore, in vivo analysis of TTR-/- mice revealed a significant decrease of the surface expression of the δ-GABA A -Rs in cerebellar granule neurons. Together, our studies identified TTR as a novel regulator of the δ-GABA A -Rs.

Original languageEnglish (US)
Article numbere0210094
JournalPloS one
Volume14
Issue number1
DOIs
StatePublished - Jan 2019

Fingerprint

prealbumin
Prealbumin
gamma-aminobutyric acid
GABA-A Receptors
gamma-Aminobutyric Acid
receptors
Neurons
neurons
granules
Brain
brain
two hybrid system techniques
Two-Hybrid System Techniques
thalamus
cerebellum
hippocampus
Thalamus
Yeast
Cerebellum
neural networks

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

@article{23b6f2865e51417484a98d3c9b14e15e,
title = "Identification of transthyretin as a novel interacting partner for the δ subunit of GABA A receptors",
abstract = "GABA A receptors (GABA A -Rs) play critical roles in brain development and synchronization of neural network activity. While synaptic GABA A -Rs can exert rapid inhibition, the extrasynaptic GABA A -Rs can tonically inhibit neuronal activity due to constant activation by ambient GABA. The δ subunit-containing GABA A -Rs are expressed abundantly in the cerebellum, hippocampus and thalamus to mediate the major tonic inhibition in the brain. While electrophysiological and pharmacological properties of the δ-GABA A -Rs have been well characterized, the molecular interacting partners of the δ-GABA A -Rs are not clearly defined. Here, using a yeast two-hybrid screening assay, we identified transthyretin (TTR) as a novel regulatory molecule for the δ-GABA A -Rs. Knockdown of TTR in cultured cerebellar granule neurons significantly decreased the δ receptor expression; whereas overexpressing TTR in cortical neurons increased the δ receptor expression. Electrophysiological analysis confirmed that knockdown or overexpression of TTR in cultured neurons resulted in a corresponding decrease or increase of tonic currents. Furthermore, in vivo analysis of TTR-/- mice revealed a significant decrease of the surface expression of the δ-GABA A -Rs in cerebellar granule neurons. Together, our studies identified TTR as a novel regulator of the δ-GABA A -Rs.",
author = "Li Zhou and Xin Tang and Xinyi Li and Yuting Bai and Buxbaum, {Joel N.} and Gong Chen",
year = "2019",
month = "1",
doi = "10.1371/journal.pone.0210094",
language = "English (US)",
volume = "14",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "1",

}

Identification of transthyretin as a novel interacting partner for the δ subunit of GABA A receptors . / Zhou, Li; Tang, Xin; Li, Xinyi; Bai, Yuting; Buxbaum, Joel N.; Chen, Gong.

In: PloS one, Vol. 14, No. 1, e0210094, 01.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Identification of transthyretin as a novel interacting partner for the δ subunit of GABA A receptors

AU - Zhou, Li

AU - Tang, Xin

AU - Li, Xinyi

AU - Bai, Yuting

AU - Buxbaum, Joel N.

AU - Chen, Gong

PY - 2019/1

Y1 - 2019/1

N2 - GABA A receptors (GABA A -Rs) play critical roles in brain development and synchronization of neural network activity. While synaptic GABA A -Rs can exert rapid inhibition, the extrasynaptic GABA A -Rs can tonically inhibit neuronal activity due to constant activation by ambient GABA. The δ subunit-containing GABA A -Rs are expressed abundantly in the cerebellum, hippocampus and thalamus to mediate the major tonic inhibition in the brain. While electrophysiological and pharmacological properties of the δ-GABA A -Rs have been well characterized, the molecular interacting partners of the δ-GABA A -Rs are not clearly defined. Here, using a yeast two-hybrid screening assay, we identified transthyretin (TTR) as a novel regulatory molecule for the δ-GABA A -Rs. Knockdown of TTR in cultured cerebellar granule neurons significantly decreased the δ receptor expression; whereas overexpressing TTR in cortical neurons increased the δ receptor expression. Electrophysiological analysis confirmed that knockdown or overexpression of TTR in cultured neurons resulted in a corresponding decrease or increase of tonic currents. Furthermore, in vivo analysis of TTR-/- mice revealed a significant decrease of the surface expression of the δ-GABA A -Rs in cerebellar granule neurons. Together, our studies identified TTR as a novel regulator of the δ-GABA A -Rs.

AB - GABA A receptors (GABA A -Rs) play critical roles in brain development and synchronization of neural network activity. While synaptic GABA A -Rs can exert rapid inhibition, the extrasynaptic GABA A -Rs can tonically inhibit neuronal activity due to constant activation by ambient GABA. The δ subunit-containing GABA A -Rs are expressed abundantly in the cerebellum, hippocampus and thalamus to mediate the major tonic inhibition in the brain. While electrophysiological and pharmacological properties of the δ-GABA A -Rs have been well characterized, the molecular interacting partners of the δ-GABA A -Rs are not clearly defined. Here, using a yeast two-hybrid screening assay, we identified transthyretin (TTR) as a novel regulatory molecule for the δ-GABA A -Rs. Knockdown of TTR in cultured cerebellar granule neurons significantly decreased the δ receptor expression; whereas overexpressing TTR in cortical neurons increased the δ receptor expression. Electrophysiological analysis confirmed that knockdown or overexpression of TTR in cultured neurons resulted in a corresponding decrease or increase of tonic currents. Furthermore, in vivo analysis of TTR-/- mice revealed a significant decrease of the surface expression of the δ-GABA A -Rs in cerebellar granule neurons. Together, our studies identified TTR as a novel regulator of the δ-GABA A -Rs.

UR - http://www.scopus.com/inward/record.url?scp=85059605849&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85059605849&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0210094

DO - 10.1371/journal.pone.0210094

M3 - Article

C2 - 30615651

AN - SCOPUS:85059605849

VL - 14

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 1

M1 - e0210094

ER -