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Identification of a Novel PSD-95/Dlg/ZO-1 (PDZ)-like Protein Interacting with the C Terminus of Presenilin-1

Xuemin Xu, Yong-chang Shi, Xian Wu, Pierluigi Gambetti, Dexin Sui, Mei-Zhen Cui
1999 Journal of Biological Chemistry  
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
more » ... ot 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.
doi:10.1074/jbc.274.46.32543 pmid:10551805 fatcat:s7jh4nut5vhx5ebnqazejcdnkq