PT  - JOURNAL ARTICLE
AU  - Lisa. L. Gomez
AU  - Shuvo Alam
AU  - Karen E. Smith
AU  - Eric Horne
AU  - Mark L. Dell'Acqua
TI  - Regulation of A-Kinase Anchoring Protein 79/150–cAMP-Dependent Protein Kinase Postsynaptic Targeting by NMDA Receptor Activation of Calcineurin and Remodeling of Dendritic Actin
AID  - 10.1523/JNEUROSCI.22-16-07027.2002
DP  - 2002 Aug 15
TA  - The Journal of Neuroscience
PG  - 7027--7044
VI  - 22
IP  - 16
4099  - http://www.jneurosci.org/content/22/16/7027.short
4100  - http://www.jneurosci.org/content/22/16/7027.full
SO  - J. Neurosci.2002 Aug 15; 22
AB  - At the postsynaptic membrane of glutamatergic synapses, the cAMP-dependent protein kinase (PKA), protein kinase C (PKC), and calcineurin (CaN) anchoring protein AKAP79/150 is recruited to NMDA and AMPA glutamate receptors by postsynaptic density (PSD)-95 family membrane-associated guanylate kinase (MAGUK) scaffold proteins. These signaling scaffold complexes may function to regulate receptor phosphorylation in synaptic plasticity. Thus, it is important to understand regulation of AKAP79/150 targeting to synapses and recruitment to PSD–MAGUK complexes. AKAP79 is targeted to the plasma membrane by an N-terminal basic domain that binds phosphatidylinositol-4,5-bisphosphate (PI-4,5-P2) and is regulated by PKC phosphorylation and calmodulin binding. Here we demonstrate that this same domain also binds F-actin in a calmodulin- and PKC-regulated manner, targets to membrane ruffles enriched in F-actin and PI-4,5-P2 in COS7 cells, and localizes to dendritic spines with F-actin and PSD–MAGUKs in hippocampal neurons. Inhibition of actin polymerization disrupted AKAP79 targeting of PKA and CaN to ruffles in COS7 cells and endogenous AKAP79/150 dendritic spine localization with PKA, CaN, and PSD–MAGUKs in neurons. AKAP79/150 postsynaptic localization was rapidly regulated by NMDA receptors through CaN activation and F-actin remodeling, further suggesting that AKAP79/150 signaling scaffold targeting depends on actin dynamics. NMDA receptor activation also regulated dendritic spine localization of PKA and CaN and association of the AKAP79/150-PKA complex with PSD–MAGUKs. Because AMPA receptor PKA phosphorylation and synaptic localization are regulated by similar NMDA receptor–CaN signaling pathways linked to hippocampal long-term depression, this regulation of AKAP79/150 postsynaptic targeting might be important for synaptic plasticity.