Abstract
The PSD-95/SAP90 family of PDZ-containing proteins is directly involved in the clustering of specific ion channels at synapses. We report that channel clustering depends on a conserved N-terminal domain of PSD-95 that mediates multimerization and disulfide linkage of PSD-95 protomers. This N-terminal multimerization domain confers channel clustering activity on a single PDZ domain. Thus, channel clustering depends on aggregation of PDZ domains achieved by head-to-head multimerization of PSD-95, rather than by concatenation of PDZ domains in PSD-95 monomers. This mechanism predicts that PSD-95 can organize heterogeneous membrane protein clusters via differential binding specificities of its three PDZ domains. PSD-95 and its relative chapsyn-110 exist as disulfide-linked complexes in rat brain, consistent with head-to-head multimerization of these proteins in vivo.
MeSH terms
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Animals
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COS Cells / chemistry
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COS Cells / physiology
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Cross-Linking Reagents / chemistry
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Cross-Linking Reagents / metabolism
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Disks Large Homolog 4 Protein
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Disulfides / chemistry*
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Disulfides / metabolism
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Gene Deletion
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Guanylate Kinases
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Intracellular Signaling Peptides and Proteins
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Ligands
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Membrane Proteins
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Molecular Sequence Data
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Mutagenesis / physiology
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Nerve Tissue Proteins / chemistry
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / physiology*
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Nucleoside-Phosphate Kinase / genetics
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Nucleoside-Phosphate Kinase / metabolism
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Potassium Channels / chemistry*
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Potassium Channels / metabolism*
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Precipitin Tests
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Protein Binding / physiology
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Protein Structure, Tertiary
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Rats
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Sequence Homology, Amino Acid
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Shaker Superfamily of Potassium Channels
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Transfection
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Tumor Suppressor Proteins
Substances
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Cross-Linking Reagents
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Disks Large Homolog 4 Protein
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Disulfides
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Dlg4 protein, rat
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Intracellular Signaling Peptides and Proteins
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Ligands
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Membrane Proteins
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Mpp2 protein, rat
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Nerve Tissue Proteins
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Potassium Channels
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Shaker Superfamily of Potassium Channels
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Tumor Suppressor Proteins
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postsynaptic density proteins
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Nucleoside-Phosphate Kinase
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DLG2 protein, human
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Guanylate Kinases