Association of an A-kinase-anchoring protein signaling scaffold with cadherin adhesion molecules in neurons and epithelial cells

• Published in: Molecular biology of the cell 2005-08, Vol.16 (8), p.3574-3590
• Main Authors: Gorski, Jessica A, Gomez, Lisa L, Scott, John D, Dell'Acqua, Mark L
• Format: Article
• Language: English
• Subjects: A Kinase Anchor Proteins; Actins - metabolism; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Animals; Binding Sites; Cadherins - metabolism; Calcineurin - metabolism; Cell Adhesion; Cell Polarity; Cells, Cultured; Dogs; Epithelial Cells - cytology; Epithelial Cells - metabolism; Fluorescence Resonance Energy Transfer; Humans; Neurons - cytology; Neurons - metabolism; Protein Binding; Rats; Receptors, N-Methyl-D-Aspartate - metabolism; Signal Transduction
• ISSN: 1059-1524; 1939-4586; 1059-1524
• DOI: 10.1091/mbc.E05-02-0134

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.