Abstract
Synaptic scaffolding molecule (S-SCAM) is a synaptic protein that consists of PDZ domains, a guanylate kinase domain, and WW domains. It interacts with N-methyl-d-aspartate receptor subunits, neuroligin, and beta-catenin. Here, we identified Axin as a novel binding partner of S-SCAM. Axin was co-immunoprecipitated with S-SCAM from rat brain, detected in the post-synaptic density fraction in rat brain subcellular fractionation, and partially co-localized with S-SCAM in neurons. The guanylate kinase domain of S-SCAM directly bound to the GSK3beta-binding region of Axin. S-SCAM formed a complex with beta-catenin and Axin, but competed with GSK3beta for Axin-binding. Thereby, S-SCAM inhibited the Axin-mediated phosphorylation of beta-catenin by GSK3beta.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing
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Animals
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Axin Protein
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Binding, Competitive / physiology
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Brain Chemistry
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Carrier Proteins / chemistry
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cells, Cultured
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Chlorocebus aethiops
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Cytoskeletal Proteins / chemistry
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Cytoskeletal Proteins / metabolism
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Glycogen Synthase Kinase 3 / chemistry
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Glycogen Synthase Kinase 3 / metabolism
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Glycogen Synthase Kinase 3 beta
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Guanylate Kinases
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Hippocampus / cytology
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Humans
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Macromolecular Substances
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Mutagenesis, Site-Directed
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Neurons / metabolism*
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Phosphorylation / drug effects
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Precipitin Tests
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Protein Binding / physiology
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Protein Structure, Tertiary / physiology
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Rats
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Repressor Proteins / chemistry
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Repressor Proteins / genetics
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Repressor Proteins / metabolism*
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Subcellular Fractions / chemistry
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Synapses / metabolism
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Trans-Activators / chemistry
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Trans-Activators / metabolism
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Transfection
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Two-Hybrid System Techniques
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beta Catenin
Substances
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Adaptor Proteins, Signal Transducing
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Axin Protein
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CTNNB1 protein, human
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Carrier Proteins
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Ctnnb1 protein, rat
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Cytoskeletal Proteins
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Macromolecular Substances
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Magi2 protein, rat
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Repressor Proteins
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Trans-Activators
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beta Catenin
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GSK3B protein, human
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Glycogen Synthase Kinase 3 beta
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Gsk3b protein, rat
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Glycogen Synthase Kinase 3
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Guanylate Kinases