Effect of presenilin 1 expression on 20S proteasome subcellular localization

Citation
G. Van Gassen et al., Effect of presenilin 1 expression on 20S proteasome subcellular localization, ALZHEIM REP, 3(2), 2000, pp. 89-95
Citations number
20
Categorie Soggetti
Neurology
Journal title
ALZHEIMERS REPORTS
ISSN journal
14616130 → ACNP
Volume
3
Issue
2
Year of publication
2000
Pages
89 - 95
Database
ISI
SICI code
1461-6130(200003/04)3:2<89:EOP1EO>2.0.ZU;2-G
Abstract
Mutations in the presenilin 1 (PSEN1) gene are a major cause of presenile a utosomal dominant Alzheimer's disease (AD). The amount of stable, proteolys ed PSEN1 fragments integrated into a larger 250 kDa membrane-bound protein complex is very tightly regulated. Proteosomal degradation of excess PSEN1 in particular polyubiquitinylated full-length PSEN1 was established in diff erent cell lines. We previously demonstrated direct physical interaction be tween PSEN1 and HC5/ZETA, two subunits of the 20S catalytic particle of the 26S proteasome. Here, we show co-localization between PSEN1 and overexpres sed HC5/ZETA and between PSEN1 and the endogenous 20S particle in the perin uclear region of PSEN1 over-expressing Neuro2a and HEK 293 cells. Co-locali zation was independent of the presence of pathogenic mutations in PSEN1. In hibition of proteasomal activity in stable PSEN1 transfected HEK 293 cells resulted in a small increase in perinuclear PSEN1 immunoreactivity, althoug h no aggresome-like structures were observed. Finally, in hippocampal brain tissue sections, in vivo intraneuronal perinuclear co-localization between PSEN1 and the 20S proteasome was observed both in PSEN1 AD and in control brains.