PMID:17189291

Citation	Chang, JW, Choi, H, Kim, HJ, Jo, DG, Jeon, YJ, Noh, JY, Park, WJ and Jung, YK (2007) Neuronal vulnerability of CLN3 deletion to calcium-induced cytotoxicity is mediated by calsenilin. Hum. Mol. Genet. 16:317-26
Abstract	Calsenilin/DREAM/KChIP3, a neuronal Ca(2+)-binding protein, has multifunctions in nucleus and cytosol. Here, we identified CLN3 as a calsenilin-binding partner whose mutation or deletion is observed in Batten disease. In vitro binding and immunoprecipitation assays show that calsenilin interacts with the C-terminal region of CLN3 and the increase of Ca(2+) concentration in vitro and in cells causes significant dissociation of calsenilin from CLN3. 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. In contrast, CLN3 deletion mutant containing the N-terminus (1-153) or (1-263), which is frequently found in Batten disease, induces the perturbation of Ca(2+) transient and fails to inhibit the cell death. In addition, the expression of calsenilin is increased in the brain tissues of CLN3 knock-out mice and SH-SY5Y/CLN3 knock-down cells. Down-regulation of CLN3 expression sensitizes SH-SY5Y cells to thapsigargin or A23187. However, additional decrease of calsenilin expression rescues the sensitivity of SH-SY5Y/CLN3 knock-down cells to Ca(2+)-mediated cell death. 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.
Links	PubMed Online version:10.1093/hmg/ddl466
Keywords	Animals; Calcium/metabolism; Calcium/pharmacology; Cell Death/drug effects; Cells, Cultured; Gene Deletion; Humans; Kv Channel-Interacting Proteins/metabolism; Kv Channel-Interacting Proteins/physiology; Membrane Glycoproteins/genetics; Membrane Glycoproteins/metabolism; Membrane Glycoproteins/physiology; Mice; Mice, Knockout; Molecular Chaperones/genetics; Molecular Chaperones/metabolism; Molecular Chaperones/physiology; Neurodegenerative Diseases/genetics; Neurodegenerative Diseases/metabolism; Neurodegenerative Diseases/pathology; Neurons/drug effects; Neurons/metabolism; Protein Binding; Protein Structure, Tertiary
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