title: Phosphorylation of calsenilin at Ser63 regulates its cleavage by caspase-3.
abstract: Calsenilin is a member of the neuronal calcium sensor (NCS) family of proteins that interacts with the presenilins. Calsenilin has been found to act as a Kv4alpha channel interactor and as a transcriptional repressor. We have recently shown that calsenilin can be cleaved by caspase-3 and that its cleavage separates the conserved calcium-binding domain from the variable N-terminal domain. Here, we demonstrate that calsenilin can be phosphorylated by casein kinase I and that its phosphorylation can be regulated by intracellular calcium. In addition, phosphorylated calsenilin is a substrate for serine/threonine protein phosphatase (PP) 1 and/or 2A. Phosphorylation within the N-terminal domain at Ser63, the major phosphorylation site of calsenilin, inhibits cleavage of the molecule by caspase-3. Given that the N-terminal domain of calsenilin is not conserved in the larger NCS family including other KChIP/CALP proteins, phosphorylation of calsenilin may regulate a functional role that is unique to this member of the superfamily.
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
authors.forename: E K
authors.initials: EK
authors.lastname: Choi
authors.forename: J S
authors.initials: JS
authors.lastname: Miller
authors.forename: N F
authors.initials: NF
authors.lastname: Zaidi
authors.forename: E
authors.initials: E
authors.lastname: Salih
authors.forename: J D
authors.initials: JD
authors.lastname: Buxbaum
authors.forename: W
authors.initials: W
authors.lastname: Wasco
mesh_terms: D000818:Animals; D000918:Antibody Specificity; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000276:immunology / Q000378:metabolism*; D047388:Casein Kinases; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D006801:Humans; D051605:Kv Channel-Interacting Proteins; D051379:Mice; D009447:Neuroblastoma; D009474:Neurons / Q000201:enzymology*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D012097:Repressor Proteins; D012694:Serine / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D002135:Calcium-Binding Proteins; C496756:Csen protein, mouse; C496749:KCNIP3 protein, human; D051605:Kv Channel-Interacting Proteins; D012097:Repressor Proteins; D012694:Serine; D011494:Protein Kinases; D047388:Casein Kinases; D010749:Phosphoprotein Phosphatases; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D002118:Calcium