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.

  • [Show abstract] [Hide abstract]
    ABSTRACT: There is increasing evidence that subcellular targeting of signaling molecules is an important means of regulating the protein kinase A (PKA) pathway. Subcellular organization of the signaling molecules in the PKA pathway insures that a signal initiated at the receptor level is transferred efficiently to a PKA substrate eliciting some cellular response. This subcellular targeting appears to regulate the function of a highly specialized cell such as the cardiac myocyte. This review focuses on A-kinase anchoring proteins (AKAPs) which are expressed in the heart. It has been determined that, of the approximately 13 different AKAPs expressed in cardiac tissue, several of these are expressed in cardiac myocytes. These AKAPs bind several PKA substrates and some appear to regulate PKA-dependent phosphorylation of these substrates. AKAP tethering of PKA may be essential for efficient regulation of cardiac muscle contraction. The ability of an AKAP to anchor PKA may be altered in the failing heart, thus compromising the ability of the myocyte to respond to stimuli which elicit the PKA pathway.
    Journal of Molecular and Cellular Cardiology 10/2004; 37(3):653-65. · 5.15 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A-Kinase Anchoring Proteins (AKAPs) orchestrate and synchronize cellular events by tethering the cAMP-dependent protein kinase (PKA) and other signaling enzymes to organelles and membranes. The control of kinases and phosphatases that are held in proximity to activators, effectors, and substrates favors the rapid dissemination of information from one cellular location to the next. This article charts the inception of the PKA-anchoring hypothesis, the characterization of AKAPs and their nomenclature, and the physiological roles of context-specific AKAP signaling complexes.
    Molecular Interventions 04/2010; 10(2):86-97. · 4.59 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Propagation of a Gaussian beam in an absorbing waveguide is analyzed for cubic–quintic and saturable media taking into account both linear and nonlinear absorption. A “collective variable approach” technique, based on trial functions, is used to solve the general nonlinear Schrodinger equation. In the absence of losses, we construct a diagram which defines regions of oscillatory and diffractive beam propagation for both types of media, and also a diagram that compares bistable behavior in such media. We show that if the linear and nonlinear absorption coefficients are small, the behavior of the oscillations of the beam width on propagation allows one to distinguish between cubic–quintic and saturable media. By reversing the sign of the linear absorption, we analyze the behavior of the beam propagation in media with gain and nonlinear absorption. In cubic–quintic media, the energy reaches a plateau for certain ratios of gain to losses, whereas for saturable media, the energy increases throughout the beam propagation.
    Optics Communications 01/2011; 284(21):5212-5217. · 1.44 Impact Factor

Full-text (2 Sources)

Available from
May 21, 2014