Human Molecular Genetics Advance Access published online on December 22, 2006
Human Molecular Genetics, doi:10.1093/hmg/ddl466
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© The Author 2006. Published by Oxford University Press. All rights reserved
Neuronal vulnerability of CLN3 deletion to calcium-induced cytotoxicity is mediated by calsenilin
1 Department of Life Science, Gwangju Institute of Science and Technology, Gwangju 500-712, Korea 2 Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, NIH Baltimore, MD 21224, USA 3 School of Biological Science/Bio-MAX Institute, Seoul National University, Shillim-Dong, Seoul 151-747, Korea
* Correspondence should be addressed: School of Biological Science, Seoul National University, Shillim-Dong, Seoul 151-747, Korea Tel: 82-2-883-0486; Fax: 82-2-887-2692; E-mail: ykjung{at}snu.ac.kr
Received December 8, 2006; Accepted December 9, 2006
Calsenilin/DREAM/KChIP3, a neuronal Ca2+-binding protein, has multi-functions 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 Ca2+ 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 [GenBank] -induced death of neuronal cells. On the contrary, CLN3 deletion mutant containing the N-terminus (1-153) or (1-263), which is frequently found in Batten disease, induces the perturbation of Ca2+ 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. [GenBank] However, additional decrease of calsenilin expression rescues the sensitivity of SH-SY5Y/CLN3 knock-down cells to Ca2+-mediated cell death. These results suggest that the vulnerability of CLN3 knock-out or CLN3 deletion (1-153)-expressing neuronal cells to Ca2+-induced cell death may be mediated by calsenilin.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J.-Y. Noh, H. Lee, S. Song, N. S. Kim, W. Im, M. Kim, H. Seo, C.-W. Chung, J.-W. Chang, R. J. Ferrante, et al. SCAMP5 Links Endoplasmic Reticulum Stress to the Accumulation of Expanded Polyglutamine Protein Aggregates via Endocytosis Inhibition J. Biol. Chem., April 24, 2009; 284(17): 11318 - 11325. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Codlin, R. L. Haines, J. Jemima, E. Burden, and S. E. Mole btn1 affects cytokinesis and cell-wall deposition by independent mechanisms, one of which is linked to dysregulation of vacuole pH J. Cell Sci., September 1, 2008; 121(17): 2860 - 2870. [Abstract] [Full Text] [PDF]
|
|