CRIPT, a Novel Postsynaptic Protein that Binds to the Third PDZ Domain of PSD-95/SAP90

• Published in: Neuron (Cambridge, Mass.) Vol. 20; no. 4; pp. 693 - 707
• Main Authors: Niethammer, Martin, Valtschanoff, Juli G, Kapoor, Tarun M, Allison, Daniel W, Weinberg, Richard J, Craig, Ann Marie, Sheng, Morgan
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.1998
• Subjects: Adaptor Proteins, Signal Transducing; Amino Acid Sequence; Animals; Arabidopsis - metabolism; Arabidopsis Proteins; Binding Sites; Brain - metabolism; Caenorhabditis - metabolism; Caenorhabditis elegans Proteins; Carrier Proteins - biosynthesis; Carrier Proteins - chemistry; Carrier Proteins - metabolism; Cells, Cultured; Cloning, Molecular; Consensus Sequence; Disks Large Homolog 4 Protein; Guanylate Kinases; Hippocampus - metabolism; Humans; Immunohistochemistry; Intracellular Signaling Peptides and Proteins; Male; Membrane Proteins - biosynthesis; Membrane Proteins - chemistry; Membrane Proteins - metabolism; Molecular Sequence Data; Nerve Tissue Proteins - chemistry; Nerve Tissue Proteins - metabolism; Neurons - metabolism; Postsynaptic density 95 protein; Rats; Rats, Sprague-Dawley; Recombinant Proteins - biosynthesis; Recombinant Proteins - chemistry; Recombinant Proteins - metabolism; SAP90-PSD95 Associated Proteins; Sequence Alignment; Sequence Homology, Amino Acid; Synapses - metabolism; Synaptosomes - metabolism; Tumor Suppressor Proteins
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/S0896-6273(00)81009-0

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.