Open AccessIdentification of transthyretin as a novel interacting partner for the δ subunit of GABAA receptors
Author(s) -
Li Zhou,
Xin Tang,
Xinyi Li,
Y. Bai,
Joel N. Buxbaum,
Gong Chen
Publication year - 2019
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0210094
Subject(s) - gabaa receptor , gabaa rho receptor , neuroscience , cerebellum , gene knockdown , protein subunit , biology , microbiology and biotechnology , receptor , chemistry , biochemistry , apoptosis , gene
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.