| First Author | Zhou L | Year | 2019 |
| Journal | PLoS One | Volume | 14 |
| Issue | 1 | Pages | e0210094 |
| PubMed ID | 30615651 | Mgi Jnum | J:269921 |
| Mgi Id | MGI:6274102 | Doi | 10.1371/journal.pone.0210094 |
| Citation | Zhou L, et al. (2019) Identification of transthyretin as a novel interacting partner for the delta subunit of GABAA receptors. PLoS One 14(1):e0210094 |
| abstractText | GABAA receptors (GABAA-Rs) play critical roles in brain development and synchronization of neural network activity. While synaptic GABAA-Rs can exert rapid inhibition, the extrasynaptic GABAA-Rs can tonically inhibit neuronal activity due to constant activation by ambient GABA. The delta subunit-containing GABAA-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 delta-GABAA-Rs have been well characterized, the molecular interacting partners of the delta-GABAA-Rs are not clearly defined. Here, using a yeast two-hybrid screening assay, we identified transthyretin (TTR) as a novel regulatory molecule for the delta-GABAA-Rs. Knockdown of TTR in cultured cerebellar granule neurons significantly decreased the delta receptor expression; whereas overexpressing TTR in cortical neurons increased the delta 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 delta-GABAA-Rs in cerebellar granule neurons. Together, our studies identified TTR as a novel regulator of the delta-GABAA-Rs. |
