The colorectal tumour suppressor APC is present in the NMDA-receptor-PSD-95 complex in the brain.
BACKGROUND
The synaptic protein PSD-95/SAP90 interacts with ion channels such as the N-methyl-D-aspartate-receptor (NMDA-R) via its PDZ domain, and is involved in their clustering. Moreover, it interacts with signalling molecules and plays an important role in coupling NMDA-R to pathways that control synaptic plasticity and learning.


RESULTS
We report that PSD-95 interacts with the adenomatous polyposis coli (APC) tumour suppressor protein via its PDZ domain. Furthermore, we found that PSD-95, NMDA-R and APC are contained in the same complex in vivo. PSD-95-NMDA-R-APC association was found to require two cysteine residues conserved in the amino-terminus of PSD-95 that are known to be critical for its multimerization.


CONCLUSIONS
Our findings suggest that the PSD-95-NMDA-R-APC complex forms due to the multimerization of PSD-95 monomers, each of which can associate with either NMDA-R or APC. It is possible that APC is involved in the regulation of ion channel clustering and/or organization of signalling molecules.
Yanai
H
H
Laboratory of Molecular and Genetic Information, Institute for Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113, Japan.
Satoh
K
K
Matsumine
A
A
Akiyama
T
T
D025601:Adenomatous Polyposis Coli Protein; D020816:Amino Acid Motifs; D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D019556:COS Cells; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000378:metabolism*; D000076122:Disks Large Homolog 4 Protein; D051528:Guanylate Kinases; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051379:Mice; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D011233:Precipitin Tests; D017434:Protein Structure, Tertiary; D016194:Receptors, N-Methyl-D-Aspartate / Q000032:analysis / Q000378:metabolism*; D020349:Surface Plasmon Resonance
D025601:Adenomatous Polyposis Coli Protein; D003598:Cytoskeletal Proteins; C501444:DLG4 protein, human; D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C120997:NR2A NMDA receptor; D009419:Nerve Tissue Proteins; D016194:Receptors, N-Methyl-D-Aspartate; C033652:postsynaptic density proteins; D051528:Guanylate Kinases