Calsenilin interacts with transcriptional co-repressor C-terminal binding protein(s)
Article first published online: 19 JUN 2006
Journal of Neurochemistry
Volume 98, Issue 4, pages 1290–1301, August 2006
How to Cite
Zaidi, N. F., Kuplast, K. G., Washicosky, K. J., Kajiwara, Y., Buxbaum, J. D. and Wasco, W. (2006), Calsenilin interacts with transcriptional co-repressor C-terminal binding protein(s). Journal of Neurochemistry, 98: 1290–1301. doi: 10.1111/j.1471-4159.2006.03972.x
- Issue published online: 19 JUN 2006
- Article first published online: 19 JUN 2006
- Received January 18, 2006; revised manuscript received April 13, 2006; accepted April 18, 2006.
- C-terminal binding protein;
- synaptic vesicles;
- transcriptional repression
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 in vivo. 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 c-fos 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 in vivo.