Association of an A-Kinase-anchoring Protein Signaling Scaffold with Cadherin Adhesion Molecules in Neurons and Epithelial Cells
| Autor: | Mark L. Dell'Acqua, John D. Scott, Lisa L. Gomez, Jessica A. Gorski |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
A-kinase-anchoring protein
endocrine system A Kinase Anchor Proteins Biology Receptors N-Methyl-D-Aspartate Adherens junction Dogs Cell Adhesion Fluorescence Resonance Energy Transfer Animals Humans Cell adhesion Protein kinase A Molecular Biology Cells Cultured Adaptor Proteins Signal Transducing Neurons Binding Sites Cadherin Cell adhesion molecule Calcineurin Cell Polarity Epithelial Cells Long-term potentiation Articles Cell Biology Cadherins Actins Rats Cell biology Synaptic plasticity Protein Binding Signal Transduction |
| Zdroj: | Molecular Biology of the Cell. 16:3574-3590 |
| ISSN: | 1939-4586 1059-1524 |
| DOI: | 10.1091/mbc.e05-02-0134 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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