Requirement of the tumour suppressor APC for the clustering of PSD-95 and AMPA receptors in hippocampal neurons.
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.
Shimomura
Atsushi
A
Department of Anatomy I, School of Medicine, Fujita Health University, Toyoake, Aichi 470-1192, Japan.
Ohkuma
Mahito
M
Iizuka-Kogo
Akiko
A
Kohu
Kazuyoshi
K
Nomura
Ryuji
R
Miyachi
Ei-ichi
E
Akiyama
Tetsu
T
Senda
Takao
T
D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D002522:Chlorocebus aethiops; D016000:Cluster Analysis; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005456:Fluorescent Dyes; D016257:Fura-2; D017491:Genes, APC / Q000502:physiology*; D047468:Immunoprecipitation; D008856:Microscopy, Fluorescence; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010957:Plasmids / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology; D018091:Receptors, AMPA / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects; D014162:Transfection; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D018690:Excitatory Amino Acid Agonists; D005456:Fluorescent Dyes; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D018091:Receptors, AMPA; C033652:postsynaptic density proteins; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D016257:Fura-2