Abstract
The synaptic protein PSD-95/SAP90 binds to and clusters a variety of membrane proteins via its two N-terminal PDZ domains. We report a novel protein, CRIPT, which is highly conserved from mammals to plants and binds selectively to the third PDZ domain (PDZ3) of PSD-95 via its C terminus. While conforming to the consensus PDZ-binding C-terminal sequence (X-S/T-X-V-COOH), residues at the -1 position and upstream of the last four amino acids of CRIPT determine its specificity for PDZ3. In heterologous cells, CRIPT causes a redistribution of PSD-95 to microtubules. In brain, CRIPT colocalizes with PSD-95 in the postsynaptic density and can be coimmunoprecipitated with PSD-95 and tubulin. These findings suggest that CRIPT may regulate PSD-95 interaction with a tubulin-based cytoskeleton in excitatory synapses.
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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Adaptor Proteins, Signal Transducing*
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Amino Acid Sequence
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Animals
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Arabidopsis / metabolism
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Arabidopsis Proteins*
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Binding Sites
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Brain / metabolism*
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Caenorhabditis / metabolism
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Caenorhabditis elegans Proteins*
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Carrier Proteins / biosynthesis
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Carrier Proteins / chemistry*
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Carrier Proteins / metabolism*
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Cells, Cultured
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Cloning, Molecular
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Consensus Sequence
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Disks Large Homolog 4 Protein
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Guanylate Kinases
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Hippocampus / metabolism
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Humans
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Immunohistochemistry
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Intracellular Signaling Peptides and Proteins
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Male
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Membrane Proteins / biosynthesis
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Membrane Proteins / chemistry*
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Membrane Proteins / metabolism*
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Molecular Sequence Data
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Nerve Tissue Proteins / chemistry
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Nerve Tissue Proteins / metabolism*
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Neurons / metabolism*
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Rats
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Rats, Sprague-Dawley
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Recombinant Proteins / biosynthesis
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Recombinant Proteins / chemistry
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Recombinant Proteins / metabolism
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SAP90-PSD95 Associated Proteins
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Sequence Alignment
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Sequence Homology, Amino Acid
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Synapses / metabolism
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Synaptosomes / metabolism*
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Tumor Suppressor Proteins
Substances
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Adaptor Proteins, Signal Transducing
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Arabidopsis Proteins
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At1g61780 protein, Arabidopsis
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CRIPT protein, human
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Caenorhabditis elegans Proteins
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Carrier Proteins
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Cript protein, rat
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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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Nerve Tissue Proteins
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Recombinant Proteins
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SAP90-PSD95 Associated Proteins
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Tumor Suppressor Proteins
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postsynaptic density proteins
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DLG2 protein, human
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Guanylate Kinases