Identification of a novel PSD-95/Dlg/ZO-1 (PDZ)-like protein interacting with the C terminus of presenilin-1.
Presenilin-1 (PS-1) is the most causative Alzheimer gene product, and its function is not well understood. In an attempt to elucidate the function of PS-1, we screened a human brain cDNA library for PS-1-interacting proteins using the yeast two-hybrid system and isolated a novel protein containing a PSD-95/Dlg/ZO-1 (PDZ)-like domain. This novel PS-1-associated protein (PSAP) shares a significant similarity with a Caenorhabditis elegans protein of unknown function. Northern blot analysis revealed that PSAP is predominantly expressed in the brain. Deletion of the first four C-terminal amino acid residues of PS-1, which contain the PDZ domain-binding motif (Gln-Phe-Tyr-Ile), reduced the binding activity of PS-1 toward PSAP 4-fold. These data suggest that PS-1 may associate with a PDZ-like domain-containing protein in vivo and thus may participate in receptor or channel clustering and intracellular signaling events in the brain.
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Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA. xmx@utk.edu
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Gambetti
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D000595:Amino Acid Sequence; D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D002460:Cell Line; D003001:Cloning, Molecular; D029721:Drosophila Proteins; D015870:Gene Expression; D006801:Humans; D019476:Insect Proteins / Q000737:chemistry*; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism*; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics; D010446:Peptide Fragments / Q000378:metabolism; D010750:Phosphoproteins / Q000737:chemistry*; D010766:Phosphorylation; D053764:Presenilin-1; D011485:Protein Binding / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D016415:Sequence Alignment; D014162:Transfection; D025521:Tumor Suppressor Proteins; D062826:Zonula Occludens-1 Protein
D029721:Drosophila Proteins; D019476:Insect Proteins; C402222:MTCH1 protein, human; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D009419:Nerve Tissue Proteins; C508853:PSEN1 protein, human; D010446:Peptide Fragments; D010750:Phosphoproteins; D053764:Presenilin-1; D012333:RNA, Messenger; C569042:TJP1 protein, human; D025521:Tumor Suppressor Proteins; D062826:Zonula Occludens-1 Protein; C033652:postsynaptic density proteins; C070350:dlg1 protein, Drosophila