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

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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

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All Science Journal Classification (ASJC) codes

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

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