Xm. Xu et al., Identification of a novel PSD-95/Dlg/ZO-1 (PDZ)-like protein interacting with the C terminus of presenilin-1, J BIOL CHEM, 274(46), 1999, pp. 32543-32546
Presenilin-1 (PS-l) is the most causative Alzheimer gene product, and its f
unction is not well understood. In an attempt to elucidate the function of
PS-l, we screened a human brain cDNA library for PS-l-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 l-associated protein (PSA
P) shares a significant similarity with a Caenorhabditis elegans protein of
unknown function. Northern blot analysis revealed that PSAP is predominant
ly expressed in the brain. Deletion of the first four C-terminal amino acid
residues of PS-l, which contain the PDZ domain-binding motif (Gln-Phe-Tyr-
Ile), reduced the binding activity of PS-l toward PSAP 4-fold. These data s
uggest that PS-l may associate with a PDZ-Iike domain-containing protein in
vivo and thus may participate in receptor or channel clustering and intrac
ellular signaling events in the brain.