Requirement of the tumour suppressor APC for the clustering of PSD-95 and AMPA receptors in hippocampal neurons

Atsushi Shimomura, Mahito Ohkuma, Akiko Iizuka-Kogo, Kazuyoshi Kohu, Ryuji Nomura, Ei Ichi Miyachi, Tetsu Akiyama, Takao Senda

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)903-912
Number of pages10
JournalEuropean Journal of Neuroscience
Volume26
Issue number4
DOIs
Publication statusPublished - 08-2007

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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