CRIPT, a novel postsynaptic protein that binds to the third PDZ domain of PSD-95/SAP90.
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.
Niethammer
M
M
Department of Neurobiology and Howard Huges Medical Institute, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA.
Valtschanoff
J G
JG
Kapoor
T M
TM
Allison
D W
DW
Weinberg
R J
RJ
Craig
A M
AM
Sheng
M
M
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D017360:Arabidopsis / Q000378:metabolism; D029681:Arabidopsis Proteins; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D002107:Caenorhabditis / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism*; D002478:Cells, Cultured; D003001:Cloning, Molecular; D016384:Consensus Sequence; D000076122:Disks Large Homolog 4 Protein; D051528:Guanylate Kinases; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D000074407:SAP90-PSD95 Associated Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013569:Synapses / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism*; D025521:Tumor Suppressor Proteins
D048868:Adaptor Proteins, Signal Transducing; D029681:Arabidopsis Proteins; C484740:At1g61780 protein, Arabidopsis; C112203:CRIPT protein, human; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; C484742:Cript protein, rat; C501444:DLG4 protein, human; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; D000074407:SAP90-PSD95 Associated Proteins; D025521:Tumor Suppressor Proteins; C033652:postsynaptic density proteins; C496468:DLG2 protein, human; D051528:Guanylate Kinases