A-kinase anchoring protein 79/150 facilitates the phosphorylation of GABAA receptors by cAMP-dependent protein kinase via selective interaction with receptor β subunits

MRC Laboratory for Molecular Cell Biology and Department of Pharmacology, University College London, Gower Street, London WCIE 6BT, UK; Howard Hughes Medical Institute, Vollum Institute, Oregon Health Sciences University, Portland, OR 97201, USA
Molecular and Cellular Neuroscience 01/2003; DOI: 10.1016/S1044-7431(02)00017-9

ABSTRACT GABAA receptors, the key mediators of fast synaptic inhibition in the brain, are predominantly constructed from α(1–6), β(1–3), γ(1–3), and δ subunit classes. Phosphorylation by cAMP-dependent protein kinase (PKA) differentially regulates receptor function dependent upon β subunit identity, but how this kinase is selectively targeted to GABAA receptor subtypes remains unresolved. Here we establish that the A-kinase anchoring protein 150 (AKAP150), directly binds to the receptor β1 and β3, but not to α1, α2, α3, α6, β2, γ2, or δ subunits. Furthermore, AKAP79/150 is critical for PKA-mediated phosphorylation of the receptor β3 subunit. Together, our observations suggest a mechanism for the selective targeting of PKA to GABAA receptor subtypes containing the β1 or β3 subunits dependent upon AKAP150. Therefore, the selective interaction of β subunits with AKAP150 may facilitate GABAA receptor subtype-specific functional modulation by PKA activity which may have profound local effects on neuronal excitation.

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