Abstract
Amyloid-β and tau protein are the two most prominent factors in the pathology of Alzheimer disease. Recent studies indicate that phosphorylated tau might affect synaptic function. We now show that endogenous tau is found at postsynaptic sites where it interacts with the PSD95-NMDA receptor complex. NMDA receptor activation leads to a selective phosphorylation of specific sites in tau, regulating the interaction of tau with Fyn and the PSD95-NMDA receptor complex. Based on our results, we propose that the physiologically occurring phosphorylation of tau could serve as a regulatory mechanism to prevent NMDA receptor overexcitation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alzheimer Disease / metabolism
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Animals
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Disks Large Homolog 4 Protein
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Gene Expression Regulation*
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HEK293 Cells
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Hippocampus / metabolism
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Humans
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Intracellular Signaling Peptides and Proteins / chemistry*
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Membrane Proteins / chemistry*
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Models, Biological
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Neurons / metabolism
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Phosphorylation
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Protein Binding
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Proto-Oncogene Proteins c-fyn / chemistry*
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Rats
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Receptors, N-Methyl-D-Aspartate / chemistry*
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Synapses / metabolism
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tau Proteins / chemistry*
Substances
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DLG4 protein, human
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Disks Large Homolog 4 Protein
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Dlg4 protein, rat
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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Receptors, N-Methyl-D-Aspartate
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tau Proteins
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Proto-Oncogene Proteins c-fyn