Disease relevance of Kcnip3

• These results demonstrate that the reduced expression of calsenilin may functionally be associated with the pathophysiology of status epilepticus [1].

High impact information on Kcnip3

• These results suggest that the vulnerability of CLN3 knock-out or CLN3 deletion (1-153)-expressing neuronal cells to Ca(2+)-induced cell death may be mediated by calsenilin [2].
• Ectopic expression of CLN3 or its deletion mutant containing only the C-terminus (153-438) and capable of binding to calsenilin suppresses thapsigargin or A23187-induced death of neuronal cells [2].
• Down-regulation of CLN3 expression sensitizes SH-SY5Y cells to thapsigargin or A23187 [2].
• Calsenilin/DREAM/KChIP3, a neuronal Ca(2+)-binding protein, has multifunctions in nucleus and cytosol [2].
• Calsenilin/DREAM/KChIP3, a member of the recoverin branch of the EF-hand superfamily, interacts with presenilins, serves as a calcium-regulated transcriptional repressor, and interacts with A-type potassium channels [3].

Biological context of Kcnip3

• Calsenilin binds Kv channels and modulates potassium conductance, playing a role in long-term potentiation as well as in other important plastic pathways [4].
• Calsenilin binds the dynorphin response element and regulates dynorphin expression, hence regulating nociception [4].
• Here we describe the biochemical and immunohistochemical characterization of calsenilin, a novel calcium binding protein that we have previously shown to interact with presenilins 1 and 2, in mouse brain [5].
• Calsenilin is a neuronal calcium binding protein that may function in calcium signaling and cell death [1].
• Therefore, these findings indicate a surprising complexity to kinase regulation of A currents, in that an interaction of two separate molecular events, alpha-subunit phosphorylation and the association of an ancillary subunit (KChIP3), are necessary for phosphorylation-dependent regulation of Kv4.2-encoded A channels by PKA [6].

Anatomical context of Kcnip3

• Finally, we demonstrated that calsenilin and CtBP are present in synaptic vesicles and can interact in vivo [7].
• KChIP3 transcripts were detected primarily in the layer V and deep layer VI of the cerebral cortex, the hippocampus, and the entire cerebellum [8].
• In addition, we have demonstrated that calsenilin is a developmentally regulated protein that is mainly present in the brain, where it localizes to both the hippocampus and cerebellum [5].
• Co-localization experiments using specific axonal and dendritic markers indicate that these processes were mainly axonal in nature, although a smaller subset of dendrites also appears to contain calsenilin [5].
• Although calsenilin has been predicted to be a soluble protein, we have found that the majority of it is tightly associated with the cytoplasmic face of intracellular membranes and that it can only be dissociated using harsh treatments such as urea [5].

Associations of Kcnip3 with chemical compounds

• The expression of calsenilin was investigated in the mouse brain after kainic acid-induced seizure and seizure-induced hippocampal neuronal cell culture system using immunostaining analysis [1].

Physical interactions of Kcnip3

• In co-immunoprecipitation studies, calsenilin also interacted with CtBP1, a CtBP2 homolog [7].
• Calsenilin interacts with presenilins, DREAM is a calcium-regulated transcriptional repressor and KChIP3 binds and modulates A-type potassium channels [9].

Other interactions of Kcnip3

• 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 [7].
• Altered Abeta formation and long-term potentiation in a calsenilin knock-out [10].
• When compared to the real-time PCR results, the SQuISH trade mark method showed almost identical relative levels of IRSp53 to Calsenilin mRNA in all three brain regions analyzed, while the riboprobe-based procedure showed a completely opposite trend [11].

Analytical, diagnostic and therapeutic context of Kcnip3

• Further functional dissection of this family of proteins will provide insight into numerous aspects of neuronal function and will illuminate the role of the calsenilin family of proteins in disease [4].

References