Calsenilin interacts with transcriptional co-repressor C-terminal binding protein(s).
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.
Zaidi
Nikhat F
NF
Department of Neurology, Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease and Harvard Medical School, Charlestown, Massachusetts 02129, USA.
Kuplast
Kristy G
KG
Washicosky
Kevin J
KJ
Kajiwara
Yuji
Y
Buxbaum
Joseph D
JD
Wasco
Wilma
W
D000429:Alcohol Oxidoreductases; D000818:Animals; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000502:physiology; D045744:Cell Line, Tumor; D002531:Cerebellum / Q000378:metabolism; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D004591:Electrophoresis, Polyacrylamide Gel; D005347:Fibroblasts / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism; D047468:Immunoprecipitation; D051605:Kv Channel-Interacting Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D009419:Nerve Tissue Proteins / Q000502:physiology; D051580:Neuronal Calcium-Sensor Proteins; D009479:Neuropeptides / Q000502:physiology; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D013572:Synaptic Vesicles / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology*; D014162:Transfection
D002135:Calcium-Binding Proteins; D056970:Co-Repressor Proteins; C496756:Csen protein, mouse; D004268:DNA-Binding Proteins; D051605:Kv Channel-Interacting Proteins; D009419:Nerve Tissue Proteins; D051580:Neuronal Calcium-Sensor Proteins; D009479:Neuropeptides; D010750:Phosphoproteins; D016760:Proto-Oncogene Proteins c-fos; D012097:Repressor Proteins; C485222:VILIP-3 protein, mouse; C101464:frequenin calcium sensor proteins; D000429:Alcohol Oxidoreductases; C111341:Ctbp2 protein, mouse; C096794:C-terminal binding protein; D006655:Histone Deacetylases