Abstract
Membrane-associated guanylate kinase-interacting protein (MAGUIN) has been identified as a protein binding postsynaptic density (PSD)-95 and synaptic scaffolding molecule (S-SCAM). MAGUIN has one sterile alpha motif, one conserved region in connector enhancer of ksr (Cnk) (CRIC), one PSD-95/Dlg-A/ZO-1 (PDZ) and one pleckstrin homology (PH) domain. There are two isoforms, MAGUIN-1 and -2. MAGUIN-1 binds the PDZ domains of PSD-95 and S-SCAM by the C-terminus, whereas MAGUIN-2 does not bind to PSD-95 or S-SCAM. Here, we have determined that MAGUIN-2 is also localized at synapses and that the synaptic localization of MAGUIN depends on the pleckstrin homology domain. The overexpressed C-terminal PDZ-binding region inhibits the synaptic targeting of PSD-95. Furthermore, the synaptic targeting of MAGUIN does not require N-methyl-d-aspartate (NMDA) receptor activity. These findings suggest that MAGUIN-1 and -2 are recruited to synapses by the PH domain and that MAGUIN-1 subsequently interacts with PSD-95 at synapses.
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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Blood Proteins / metabolism
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Carrier Proteins / metabolism*
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Cell Differentiation / physiology*
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Cells, Cultured
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Cricetinae
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Dendrites / metabolism
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Dendrites / ultrastructure
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Disks Large Homolog 4 Protein
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Excitatory Amino Acid Antagonists / pharmacology
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Female
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Fetus
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Green Fluorescent Proteins
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Hippocampus / embryology*
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Hippocampus / metabolism
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Hippocampus / ultrastructure
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Indicators and Reagents / metabolism
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Intracellular Signaling Peptides and Proteins
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Luminescent Proteins / metabolism
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Macromolecular Substances
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Membrane Proteins
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Nerve Tissue Proteins / metabolism*
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Neurons / metabolism*
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Neurons / ultrastructure
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Phosphoproteins / metabolism
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Pregnancy
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Protein Structure, Tertiary / physiology
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Rats
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Receptors, Glutamate / drug effects
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Receptors, Glutamate / metabolism
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Synaptic Membranes / metabolism*
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Synaptic Membranes / ultrastructure
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Synaptic Transmission / physiology*
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Synaptophysin / metabolism
Substances
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Adaptor Proteins, Signal Transducing
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Blood Proteins
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Carrier Proteins
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Cnksr2 protein, rat
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Disks Large Homolog 4 Protein
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Dlg4 protein, rat
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Excitatory Amino Acid Antagonists
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Indicators and Reagents
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Intracellular Signaling Peptides and Proteins
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Luminescent Proteins
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Macromolecular Substances
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Membrane Proteins
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Nerve Tissue Proteins
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Phosphoproteins
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Receptors, Glutamate
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Synaptophysin
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platelet protein P47
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postsynaptic density proteins
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Green Fluorescent Proteins