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- Title
Degradation of nicastrin involves both proteasome and lysosome.
- Authors
Guiqiong He; Hong Qing; Yigang Tong; Fang Cai; Ishiura, Shoichi; Weihong Song
- Abstract
The glycoprotein nicastrin (NCT) is an essential component of the γ-secretase complex, a high molecular weight complex which also contains the presenilin proteins, Aph-1 and Pen-2. The γ-secretase complex is not only involved in APP processing but also in the processing of an increasing number of other type I integral membrane proteins. As the largest subunit of the γ-secretase complex, NCT plays a crucial role in its activation. Considerable information exists on the distribution, structure and function of NCT; however, little is known of its proteolysis. The present study is aimed at exploring the molecular mechanism of NCT degradation. We found that either proteasomal or lysosomal inhibition can significantly increase the levels of both endogenous and exogenous NCT in various cell lines, and the effect of these inhibitions on NCT was time- and dose-dependent. Immunofluorescent microscopic analysis revealed that NCT accumulates in the ER and Golgi apparatus after proteasomal inhibition, while lysosomal inhibition leads to the accumulation of NCT in the lysosomal apparatus. Co-immunoprecipitation can pull down both NCT and ubiquitin. Taken together, our results demonstrate that NCT degradation involves both the proteasome and the lysosome.
- Subjects
GLYCOPROTEINS; LYSOSOMES; PROTEOLYSIS; PRESENILINS; PROTEINS
- Publication
Journal of Neurochemistry, 2007, Vol 101, Issue 4, p982
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/j.1471-4159.2007.04449.x