PT  - JOURNAL ARTICLE
AU  - Terunuma, Miho
AU  - Xu, Jianwei
AU  - Vithlani, Mansi
AU  - Sieghart, Werner
AU  - Kittler, Josef
AU  - Pangalos, Menelas
AU  - Haydon, Philip G.
AU  - Coulter, Douglas A.
AU  - Moss, Stephen J.
TI  - Deficits in Phosphorylation of GABA<sub>A</sub> Receptors by Intimately Associated Protein Kinase C Activity Underlie Compromised Synaptic Inhibition during Status Epilepticus
AID  - 10.1523/JNEUROSCI.4346-07.2008
DP  - 2008 Jan 09
TA  - The Journal of Neuroscience
PG  - 376--384
VI  - 28
IP  - 2
4099  - http://www.jneurosci.org/content/28/2/376.short
4100  - http://www.jneurosci.org/content/28/2/376.full
SO  - J. Neurosci.2008 Jan 09; 28
AB  - Status epilepticus (SE) is a progressive and often lethal human disorder characterized by continuous or rapidly repeating seizures. Of major significance in the pathology of SE are deficits in the functional expression of GABAA receptors (GABAARs), the major sites of fast synaptic inhibition in the brain. We demonstrate that SE selectively decreases the phosphorylation of GABAARs on serine residues 408/9 (S408/9) in the β3 subunit by intimately associated protein kinase C isoforms. Dephosphorylation of S408/9 unmasks a basic patch-binding motif for the clathrin adaptor AP2, enhancing the endocytosis of selected GABAAR subtypes from the plasma membrane during SE. In agreement with this, enhancing S408/9 phosphorylation or selectively blocking the binding of the β3 subunit to AP2 increased GABAAR cell surface expression levels and restored the efficacy of synaptic inhibition in SE. Thus, enhancing phosphorylation of GABAARs or selectively blocking their interaction with AP2 may provide novel therapeutic strategies to ameliorate SE.