Abstract
CRIPT is a postsynaptic protein that binds selectively to the third PDZ domain (PDZ3) of PSD-95. Here we show that CRIPT also binds directly to microtubules, thereby linking PSD-95 to the microtubule cytoskeleton. Disrupting the CRIPT-PSD-95 interaction in cultured hippocampal neurons with a PDZ3-specific peptide prevented the association of PSD-95 with microtubules and inhibited the synaptic clustering of PSD-95, chapsyn-110/PSD-93 and GKAP (a PSD-95-binding protein). However, the number of synapses and the synaptic clustering of NMDA receptors were unaffected, suggesting that PSD-95-family proteins are not essential for the maintenance of synapses and the synaptic localization of NMDA receptors.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Motifs
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Amino Acid Sequence
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Amino Acid Substitution
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Animals
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COS Cells
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Calcium-Calmodulin-Dependent Protein Kinases*
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Carrier Proteins / antagonists & inhibitors
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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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Guanylate Kinases
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Hippocampus / cytology
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Membrane Proteins / chemistry
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Microtubule-Associated Proteins / metabolism
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Microtubules / drug effects
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Microtubules / metabolism*
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Molecular Sequence Data
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Nerve Tissue Proteins / antagonists & inhibitors
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Nerve Tissue Proteins / chemistry
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Neurons / cytology
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Neurons / drug effects
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Neurons / enzymology
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Neurons / metabolism
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Nucleoside-Phosphate Kinase / antagonists & inhibitors
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Nucleoside-Phosphate Kinase / metabolism
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Peptide Fragments / chemistry
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Peptide Fragments / metabolism
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Peptide Fragments / pharmacology
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Receptors, N-Methyl-D-Aspartate / metabolism
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / metabolism
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Recombinant Fusion Proteins / pharmacology
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SAP90-PSD95 Associated Proteins
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Synapses / drug effects
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Synapses / enzymology
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Synapses / metabolism*
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Synaptophysin / metabolism
Substances
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Carrier Proteins
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Membrane Proteins
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Microtubule-Associated Proteins
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Nerve Tissue Proteins
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Peptide Fragments
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Receptors, N-Methyl-D-Aspartate
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Recombinant Fusion Proteins
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SAP90-PSD95 Associated Proteins
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Synaptophysin
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postsynaptic density proteins
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CASK kinases
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Calcium-Calmodulin-Dependent Protein Kinases
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Nucleoside-Phosphate Kinase
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Guanylate Kinases