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 s uch as the N-methyl-D-aspartate-receptor (NMDA-R) via its PDZ domain, and i s involved in their clustering. Moreover, it interacts with signalling mole cules and plays an important role in coupling NMDA-R to pathways that contr ol synaptic plasticity and learning. Results: We report that PSD-95 interacts with the adenomatous polyposis col i (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 conse rved in the amino-terminus of PSD-95 that are known to be critical for its multimerization. Conclusion: Our findings suggest that the PSD-95-NMDA-R-APC complex forms d ue to the multimerization of PSD-95 monomers, each of which can associate w ith either NMDA-R or APC. It is possible that APC is involved in the regula tion of ion channel clustering and/or organization of signalling molecules.