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The colorectal tumour suppressor APC is present in the NMDA-receptor-PSD-95 complex in the brain
H Yanai1, K Satoh, A Matsumine
1Laboratory of Molecular and Genetic Information, Institute for Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113, Japan.
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.
Conclusion:
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.