APC affects AMPA signal transduction via clustering of PSD-95

Abstract

The adenomatous polyposis coli (APC) tumor suppressor gene is linked to the development of familial adenomatous polyposis and sporadic colorectal tumors. Though APC is highly expressed in the central nervous system (CNS) and directly binds to PSD-95 through the extreme C terminus of APC, the significance of the interaction between APC and PSD-95 in CNS remains unknown. In this study, we investigated whether APC associates neural signal transduction via clustering of PSD-95 in neurons. We performed the calcium imaging and the patch clamp recording in 9-11 days cultured hippocampal neurons. Bath application of 1 μM AMPA increased intracellular calcium concentration in control cells. However, this response was inhibited in the dominant negative (APC-C72) cells, which were overexpressed a dominant negative molecule (APC-C72) that could disrupt the interaction between APC and PSD-95. Under patch clamp condition, no interactions were observed in the neighboring APC-C72 cells. These results suggest that APC may affect AMPA signal transduction via clustering of PSD-95. [Jpn J Physiol 54 Suppl:S147 (2004)]