Neuroscience 2003 Abstract
| Presentation Number: | 471.12 |
|---|---|
| Abstract Title: | The impact of genetic disruption of PKA-AKAP interaction on PKA localization in hippocampus. |
| Authors: |
McDonough, C. B.*1
; Nie, T.1
; Abel, T.1
1Dept. Biol, Univ. Pennsylvania, Philadelphia, PA |
| Primary Theme and Topics |
Synaptic Transmission and Excitability - Intracellular Signaling Pathways -- Other |
| Session: |
471. Signal Transduction Mechanisms Poster |
| Presentation Time: | Monday, November 10, 2003 4:00 PM-5:00 PM |
| Location: | Morial Convention Center - Hall F-I, Board # D43 |
| Keywords: | cAMP-dependent protein kinase, a-kinase anchoring proteins, hippocampus, cAMP signalling |
A-kinase anchoring proteins (AKAPs) are a large family proteins that share the ability to bind the regulatory subunits of cAMP-dependent protein kinase (PKA). AKAP-PKA interactions tether PKA to various intracellular loci, keeping PKA in close proximity to its substrates. AKAP complexes also contain protein phosphatases and phosphodiesterases. Disruption of AKAP-PKA interactions has been shown to alter PKA signaling in cultured cells. Our laboratory has generated transgenic mice that express an inhibitory fragment of Ht31, an AKAP cloned from human thyroid tissue, in forebrain neurons. Biochemical characterization of these animals demonstrated disruption of known AKAP complexes including PKA and protein phosphatase 1. These animals also display alterations in hippocampal and amygdala function as assessed by behavioral characterization in the spatial version of the Morris Water Maze and fear conditioning (Nie and Abel, SFN 2002). In this series of experiments we characterize the impact of transgenic Ht31 expression on PKA localization. Because immunoprecipitation data demonstrated that AKAP-PKA complexes were disrupted as a result of Ht31 expression, we used confocal microscopy and immunofluorescence to examine the impact of expressing Ht31 on localization of the RII-alpha subunit of PKA in the hippocampus. In hippocampi of wildtype mice, RII-alpha subunits display punctate labeling near the soma and in apical dendrites of CA1 pyramidal neurons. In animals expressing Ht31, this staining pattern was more diffuse in the soma and apical dendrites. These data are consistent with a reduction in anchoring of PKA as a result of transgenic Ht31 expression. Future experiments will examine the impact of blocking PKA-AKAP interactions on nuclear PKA signaling in these transgenic animals.
Supported by Merck Foundation, NIH, the Packard Foundation, the University of Pennsylvania Research Foundation and the Whitehall Foundation.
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2003 Neuroscience Meeting Planner. New Orleans, LA: Society for Neuroscience, 2003. Online.
Copyright © 2003-2026 Society for Neuroscience; all rights reserved. Permission to republish any abstract or part of any abstract in any form must be obtained in writing by SfN office prior to publication.
