UCL logo

UCL Discovery

UCL home » Library Services » Electronic resources » UCL Discovery

Identification of the sites for CaMK-II-dependent phosphorylation of GABA(A) receptors

Houston, CM; Lee, HHC; Hosie, AM; Moss, SJ; Smart, TG; (2007) Identification of the sites for CaMK-II-dependent phosphorylation of GABA(A) receptors. J BIOL CHEM , 282 (24) 17855 - 17865. 10.1074/jbc.M611533200. Gold open access

Abstract

Phosphorylation can affect both the function and trafficking of GABA(A) receptors with significant consequences for neuronal excitability. Serine/threonine kinases can phosphorylate the intracellular loops between M3-4 of GABA(A) receptor beta and gamma subunits thereby modulating receptor function in heterologous expression systems and in neurons (1, 2). Specifically, CaMK-II has been demonstrated to phosphorylate the M3 -4 loop of GABAA receptor subunits expressed as GST fusion proteins (3, 4). It also increases the amplitude of GABAA receptor-mediated currents in a number of neuronal cell types (5 -7). To identify which substrate sites CaMK-II might phosphorylate and the consequent functional effects, we expressed recombinant GABAA receptors in NG108-15 cells, which have previously been shown to support CaMK-II modulation of GABAA receptors containing the beta 3 subunit (8). We now demonstrate that CaMK-II mediates its effects on alpha 1 beta 3 receptors via phosphorylation of Ser(383) within the M3-4 domain of the beta subunit. Ablation of beta 3 subunit phosphorylation sites for CaMK-II revealed that for alpha beta gamma receptors, CaMK-II has a residual effect on GABA currents that is not mediated by previously identified sites of CaMK-II phosphorylation. This residual effect is abolished by mutation of tyrosine phosphorylation sites, Tyr(365) and Tyr(367), on the gamma 2S subunit, and by the tyrosine kinase inhibitor genistein. These results suggested that CaMK-II is capable of directly phosphorylating GABAA receptors and activating endogenous tyrosine kinases to phosphorylate the gamma 22 subunit in NG108-15 cells. These findings were confirmed in a neuronal environment by expressing recombinant GABAA receptors in cerebellar granule neurons.

Type: Article
Title: Identification of the sites for CaMK-II-dependent phosphorylation of GABA(A) receptors
Open access status: An open access publication
DOI: 10.1074/jbc.M611533200
Keywords: GAMMA-AMINOBUTYRIC-ACID, PROTEIN-KINASE-C, VASCULAR SMOOTH-MUSCLE, LONG-TERM POTENTIATION, D-ASPARTATE RECEPTOR, TYROSINE PHOSPHORYLATION, A RECEPTOR, INTRACELLULAR DOMAINS, SYNAPTIC-TRANSMISSION, COUPLED RECEPTORS
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: http://discovery.ucl.ac.uk/id/eprint/177453
Downloads since deposit
0Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item