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Association of an A-kinase-anchoring pro ... in neurons and epithelial cells
Association of an A-kinase-anchoring protein signaling scaffold with cadherin adhesion molecules in neurons and epithelial cells
2229
A-kinase-anchoring protein (AKAP) 79/150 organizes a scaffold of cAMP-dependent protein kinase (PKA), protein kinase C (PKC), and protein phosphatase 2B/calcineurin that regulates phosphorylation pathways underlying neuronal long-term potentiation and long-term depression (LTD) synaptic plasticity. AKAP79/150 postsynaptic targeting requires three N-terminal basic domains that bind F-actin and acidic phospholipids. Here, we report a novel interaction of these domains with cadherin adhesion molecules that are linked to actin through beta-catenin (beta-cat) at neuronal synapses and epithelial adherens junctions. Mapping the AKAP binding site in cadherins identified overlap with beta-cat binding; however, no competition between AKAP and beta-cat binding to cadherins was detected in vitro. Accordingly, AKAP79/150 exhibited polarized localization with beta-cat and cadherins in epithelial cell lateral membranes, and beta-cat was present in AKAP-cadherin complexes isolated from epithelial cells, cultured neurons, and rat brain synaptic membranes. Inhibition of epithelial cell cadherin adhesion and actin polymerization redistributed intact AKAP-cadherin complexes from lateral membranes to intracellular compartments. In contrast, stimulation of neuronal pathways implicated in LTD that depolymerize postsynaptic F-actin disrupted AKAP-cadherin interactions and resulted in loss of the AKAP, but not cadherins, from synapses. This neuronal regulation of AKAP79/150 targeting to cadherins may be important in functional and structural synaptic modifications underlying plasticity.
Gorski JA, Gomez LL, Scott JD, Dell'Acqua ML
Molecular biology of the cell
2005-08-01 00:00
16
8
3574-90
Actins,Adaptor Proteins, Signal Transducing,Animals,Binding Sites,Cadherins,Calcineurin,Cell Adhesion,Cell Polarity,Cells, Cultured,Dogs,Epithelial Cells,Fluorescence Resonance Energy Transfer,Humans,Neurons,Protein Binding,Rats,Receptors, N-Methyl-D-Aspartate,Signal Transduction,Actins,Adaptor Proteins, Signal Transducing,Akap5 protein, rat,Cadherins,Receptors, N-Methyl-D-Aspartate,Calcineurin
Department of Pharmacology, University of Colorado at Denver and Health Sciences Center, Aurora, CO 80045, USA.
Mol. Biol. Cell
NIGMS GM-48231, NINDS NS-40701
1059-1524
10.1091/mbc.E05-02-0134
E05-02-0134
0
False
15930126
