QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, March 1, 2006, 26(9):2391-2402; doi:10.1523/JNEUROSCI.3092-05.2006

This Article Full Text Full Text (PDF) Supplemental data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (19) Citing Articles via Google Scholar Google Scholar Articles by Smith, K. E. Articles by Dell’Acqua, M. L. Search for Related Content PubMed PubMed Citation Articles by Smith, K. E. Articles by Dell’Acqua, M. L.

 Previous Article  |  Next Article 

Cellular/Molecular
cAMP-Dependent Protein Kinase Postsynaptic Localization Regulated by NMDA Receptor Activation through Translocation of an A-Kinase Anchoring Protein Scaffold Protein

Karen E. Smith,¹ Emily S. Gibson,¹ and Mark L. Dell’Acqua^1,2

¹Department of Pharmacology and ²Program in Neuroscience, University of Colorado at Denver and Health Sciences Center, Aurora, Colorado 80045

Correspondence should be addressed to Mark L. Dell’Acqua, Department of Pharmacology, University of Colorado at Denver and Health Sciences Center at Fitzsimons, P.O. Box 6511, Mail Stop 8303, Aurora, CO 80045-0508. Email: Mark.DellAcqua{at}uchsc.edu

NMDA receptor-dependent long-term potentiation and long-term depression (LTD) involve changes in AMPA receptor activity and postsynaptic localization that are in part controlled by glutamate receptor 1 (GluR1) subunit phosphorylation. The scaffolding molecule A-kinase anchoring protein (AKAP)79/150 targets both the cAMP-dependent protein kinase (PKA) and protein phosphatase 2B/calcineurin (PP2B/CaN) to AMPA receptors to regulate GluR1 phosphorylation. Here, we report that brief NMDA receptor activation leads to persistent redistribution of AKAP79/150 and PKA-RII, but not PP2B/CaN, from postsynaptic membranes to the cytoplasm in hippocampal slices. Similar to LTD, AKAP79/150 redistribution requires PP2B/CaN activation and is accompanied by GluR1 dephosphorylation and internalization. Using fluorescence resonance energy transfer microscopy in hippocampal neurons, we demonstrate that PKA anchoring to AKAP79/150 is required for NMDA receptor regulation of PKA-RII localization and that movement of AKAP–PKA complexes underlies PKA redistribution. These findings suggest that LTD involves removal of AKAP79/150 and PKA from synapses in addition to activation of PP2B/CaN. Movement of AKAP79/150–PKA complexes from the synapse could further favor the actions of phosphatases in maintaining dephosphorylation of postsynaptic substrates, such as GluR1, that are important for LTD induction and expression. In addition, our observations demonstrate that AKAPs serve not solely as stationary anchors in cells but also as dynamic signaling components.

Key words: A-kinase anchoring proteins; AMPA receptor; LTD; PKA; synaptic plasticity; FRET

---

Received July 26, 2005; revised Jan. 18, 2006; accepted Jan. 19, 2006.

Correspondence should be addressed to Mark L. Dell’Acqua, Department of Pharmacology, University of Colorado at Denver and Health Sciences Center at Fitzsimons, P.O. Box 6511, Mail Stop 8303, Aurora, CO 80045-0508. Email: Mark.DellAcqua{at}uchsc.edu

This article has been cited by other articles:

				T. A. Blanpied, J. M. Kerr, and M. D. Ehlers Structural plasticity with preserved topology in the postsynaptic protein network PNAS, August 26, 2008; 105(34): 12587 - 12592. [Abstract] [Full Text] [PDF]

				U. Narayanan, V. Nalavadi, M. Nakamoto, G. Thomas, S. Ceman, G. J. Bassell, and S. T. Warren S6K1 Phosphorylates and Regulates Fragile X Mental Retardation Protein (FMRP) with the Neuronal Protein Synthesis-dependent Mammalian Target of Rapamycin (mTOR) Signaling Cascade J. Biol. Chem., July 4, 2008; 283(27): 18478 - 18482. [Abstract] [Full Text] [PDF]

				S. J. Tavalin AKAP79 Selectively Enhances Protein Kinase C Regulation of GluR1 at a Ca2+-Calmodulin-dependent Protein Kinase II/Protein Kinase C Site J. Biol. Chem., April 25, 2008; 283(17): 11445 - 11452. [Abstract] [Full Text] [PDF]

				J. C. Trinidad, A. Thalhammer, C. G. Specht, A. J. Lynn, P. R. Baker, R. Schoepfer, and A. L. Burlingame Quantitative Analysis of Synaptic Phosphorylation and Protein Expression Mol. Cell. Proteomics, April 1, 2008; 7(4): 684 - 696. [Abstract] [Full Text] [PDF]

				J. L. Hellier, D. R. Grosshans, S. J. Coultrap, J. P. Jones, P. Dobelis, M. D. Browning, and K. J. Staley NMDA Receptor Trafficking at Recurrent Synapses Stabilizes the State of the CA3 Network J Neurophysiol, November 1, 2007; 98(5): 2818 - 2826. [Abstract] [Full Text] [PDF]

				J. Song, G. Shen, L. J. Greenfield Jr., and E. I. Tietz Benzodiazepine Withdrawal-Induced Glutamatergic Plasticity Involves Up-Regulation of GluR1-Containing {alpha}-Amino-3-hydroxy-5-methylisoxazole-4-propionic Acid Receptors in Hippocampal CA1 Neurons J. Pharmacol. Exp. Ther., August 1, 2007; 322(2): 569 - 581. [Abstract] [Full Text] [PDF]

				E. A. Horne and M. L. Dell'Acqua Phospholipase C Is Required for Changes in Postsynaptic Structure and Function Associated with NMDA Receptor-Dependent Long-Term Depression J. Neurosci., March 28, 2007; 27(13): 3523 - 3534. [Abstract] [Full Text] [PDF]

				W. J. Brackenbury and M. B. A. Djamgoz Activity-dependent regulation of voltage-gated Na+ channel expression in Mat-LyLu rat prostate cancer cell line J. Physiol., June 1, 2006; 573(2): 343 - 356. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help