Present address: Department of Molecular Immunology, Institute of Development, Ageing, and Cancer, Tohoku University, Sendai 980–8575, Japan.
Requirement of the tumour suppressor APC for the clustering of PSD-95 and AMPA receptors in hippocampal neurons
Article first published online: 15 AUG 2007
European Journal of Neuroscience
Volume 26, Issue 4, pages 903–912, August 2007
How to Cite
Shimomura, A., Ohkuma, M., Iizuka-Kogo, A., Kohu, K., Nomura, R., Miyachi, E.-i., Akiyama, T. and Senda, T. (2007), Requirement of the tumour suppressor APC for the clustering of PSD-95 and AMPA receptors in hippocampal neurons. European Journal of Neuroscience, 26: 903–912. doi: 10.1111/j.1460-9568.2007.05723.x
- Issue published online: 15 AUG 2007
- Article first published online: 15 AUG 2007
- Received 31 October 2006, revised 7 June 2007, accepted 28 June 2007
- glutamatergic synapse;
- NMDA receptor
Mutations in the adenomatous polyposis coli (APC) gene are associated with familial adenomatous polyposis and sporadic colorectal tumours. The APC gene is expressed ubiquitously in various tissues, especially throughout the large intestine and central nervous system (CNS). In the CNS, the expression of the APC protein is highest during embryonic and early postnatal development. APC associates through its C-terminal region with postsynaptic density (PSD)-95, a neuronal protein that participates in synapse development. Here, we examined the involvement of APC in synaptogenesis. In cultured hippocampal neurons, both overexpression of a dominant-negative construct that disrupts the APC–PSD-95 interaction and knockdown of APC expression using small interfering RNA (siRNA) inhibited the clustering of PSD-95 and a glutamate receptor subunit, and reduced alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA)-induced activity of AMPA receptors; however, the clustering of an N-methyl-d-aspartate (NMDA) receptor subunit was unaffected. These results are suggestive of APC involvement in the development of glutamatergic synapses.