Calsenilin is degraded by the ubiquitin-proteasome pathway.

Abstract

Calsenilin, a neuronal calcium binding protein that has been shown to have multiple functions in the cell, interacts with presenilin 1 (PS1) and presenilin 2 (PS2), represses gene transcription and binds to A-type voltage-gated potassium channels. In addition, increased levels of calsenilin are observed in the brains of Alzheimer's disease and epilepsy patients. The present study was designed to investigate the molecular mechanism of calsenilin degradation pathways in cultured cells. Here, we demonstrate that inhibition of the ubiquitin-proteasomal pathway (UPP) but not lysosomal pathway markedly increased the expression levels of calsenilin. Immunofluorescence analysis revealed that following proteasomal inhibition calsenilin accumulated in the endoplasmic reticulum (ER) and Golgi, while lysosomal inhibition had no effect on calsenilin localization. In addition, we found the change of subcellular localization of PS1 from diffuse pattern to punctuate staining pattern in the ER and perinuclear region in the presence of calsenilin. These findings suggest that calsenilin degradation is primarily mediated by the UPP and that impairment in the UPP may contribute to the involvement of calsenilin in disease-associated neurodegeneration.

• Authors: Changhwan Jang, Jin-Kyu Choi, EunYoung Kim, Eun-Su Park, Wilma Wasco, Joseph D Buxbaum, Yong-Sun Kim, Eun-Kyoung Choi
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 405 Issue 2 Pg. 180-5 (Feb 11 2011) ISSN: 1090-2104 [Electronic] United States
• PMID: 21216226 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Cysteine Proteinase Inhibitors
• KCNIP3 protein, human
• Kv Channel-Interacting Proteins
• Leupeptins
• Proteasome Inhibitors
• Repressor Proteins
• Ubiquitin
• Proteasome Endopeptidase Complex
• benzyloxycarbonylleucyl-leucyl-leucine aldehyde

Topics

• Cell Line, Tumor
• Cysteine Proteinase Inhibitors (pharmacology)
• Endoplasmic Reticulum (metabolism)
• Golgi Apparatus (metabolism)
• Humans
• Kv Channel-Interacting Proteins (metabolism)
• Leupeptins (pharmacology)
• Lysosomes (drug effects, metabolism)
• Neurodegenerative Diseases (metabolism)
• Proteasome Endopeptidase Complex (metabolism)
• Proteasome Inhibitors
• Repressor Proteins (metabolism)
• Ubiquitin (metabolism)
• Ubiquitination