| First Author | Nathanson AJ | Year | 2019 |
| Journal | Cell Rep | Volume | 28 |
| Issue | 3 | Pages | 670-681.e8 |
| PubMed ID | 31315046 | Mgi Jnum | J:288423 |
| Mgi Id | MGI:6432142 | Doi | 10.1016/j.celrep.2019.06.014 |
| Citation | Nathanson AJ, et al. (2019) Identification of a Core Amino Acid Motif within the alpha Subunit of GABAARs that Promotes Inhibitory Synaptogenesis and Resilience to Seizures. Cell Rep 28(3):670-681.e8 |
| abstractText | The fidelity of inhibitory neurotransmission is dependent on the accumulation of gamma-aminobutyric acid type A receptors (GABAARs) at the appropriate synaptic sites. Synaptic GABAARs are constructed from alpha(1-3), beta(1-3), and gamma2 subunits, and neurons can target these subtypes to specific synapses. Here, we identify a 15-amino acid inhibitory synapse targeting motif (ISTM) within the alpha2 subunit that promotes the association between GABAARs and the inhibitory scaffold proteins collybistin and gephyrin. Using mice in which the ISTM has been introduced into the alpha1 subunit (Gabra1-2 mice), we show that the ISTM is critical for axo-axonic synapse formation, the efficacy of GABAergic neurotransmission, and seizure sensitivity. The Gabra1-2 mutation rescues seizure-induced lethality in Gabra2-1 mice, which lack axo-axonic synapses due to the deletion of the ISTM from the alpha2 subunit. Taken together, our data demonstrate that the ISTM plays a critical role in promoting inhibitory synapse formation, both in the axonic and somatodendritic compartments. |
