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
N1 - Publisher Copyright:
© 2019 Zhou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.
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U2 - 10.1371/journal.pone.0210094
DO - 10.1371/journal.pone.0210094
M3 - Article
C2 - 30615651
AN - SCOPUS:85059605849
SN - 1932-6203
VL - 14
JO - PloS one
JF - PloS one
IS - 1
M1 - e0210094
ER -