Description:
<jats:title>Abstract</jats:title><jats:p>Calsenilin/potassium channel‐interacting protein (KChIP)3/ downstream regulatory element sequence antagonist modulator (DREAM) is a neuronal calcium‐binding protein that has been shown to have multiple functions in the cell, including the regulation of presenilin processing, repression of transcription and modulation of A‐type potassium channels. To gain a better understanding of the precise role of calsenilin in specific cellular compartments, an interactor hunt for proteins that bind to the N‐terminal domain of calsenilin was carried out. Using a yeast two‐hybrid system and co‐immunoprecipitation studies, we have identified the transcriptional co‐repressor C‐terminal binding protein (CtBP)2 as an interactor for calsenilin and have shown that the two proteins can interact <jats:italic>in vivo</jats:italic>. In co‐immunoprecipitation studies, calsenilin also interacted with CtBP1, a CtBP2 homolog. Our data also showed a calsenilin‐dependent increase in c‐fos protein levels in CtBP knockout fibroblasts, suggesting that CtBP may modulate the transcriptional repression of <jats:italic>c‐fos</jats:italic> by calsenilin. Furthermore, the finding that histone deacetylase protein and activity were associated with the calsenilin–CtBP immunocomplex suggests a mechanism by which calsenilin–CtBP may act to repress transcription. Finally, we demonstrated that calsenilin and CtBP are present in synaptic vesicles and can interact <jats:italic>in vivo</jats:italic>.</jats:p>