Overexpression of sigma-1 receptor inhibits ADAM10 and ADAM17 mediated shedding in vitro.
10.1007/s13238-012-2006-9
- Author:
Juan LI
1
;
Bin LIU
;
Xiaofei GAO
;
Zhixing MA
;
Tianyi CAOSONG
;
Yan-ai MEI
;
Yufang ZHENG
Author Information
1. School of Life Sciences, Fudan University, Shanghai, 200433, China.
- Publication Type:Journal Article
- MeSH:
ADAM Proteins;
metabolism;
ADAM10 Protein;
ADAM17 Protein;
Amyloid Precursor Protein Secretases;
metabolism;
Animals;
Betacellulin;
COS Cells;
Cercopithecus aethiops;
Gene Expression;
HEK293 Cells;
Heparin-binding EGF-like Growth Factor;
Humans;
Intercellular Signaling Peptides and Proteins;
metabolism;
Membrane Microdomains;
metabolism;
Membrane Proteins;
metabolism;
Receptors, sigma;
agonists;
metabolism
- From:
Protein & Cell
2012;3(2):153-159
- CountryChina
- Language:English
-
Abstract:
The sigma-1 receptor is a molecular chaperone protein highly enriched in the brain. Recent studies linked it to many diseases, such as drug addition, Alzheimer's disease, stroke, depression, and even cancer. Sigma-1 receptor is enriched in lipid rafts, which are membrane microdomains essential in signaling processes. One of those signaling processes is ADAM17- and ADAM10-dependent ectodomain shedding. By using an alkaline phosphatase tagged substrate reporter system, we have shown that ADAM10-dependent BTC shedding was very sensitive to both membrane lipid component change and sigma-1 receptor agonist DHEAS treatment while ADAM17-dependent HB-EGF shedding was not; and overexpression of sigma-1 receptor diminished ADAM17- and ADAM10-dependent shedding. Our results indicate that sigma-1 receptor plays an important role in modifying the function of transmembrane proteases.
