Overexpression of sigma-1 receptor inhibits ADAM10 and ADAM17 mediated shedding in vitro.
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.
School of Life Sciences, Fudan University, Shanghai, 200433, China.
Juan
J
Li
Bin
B
Liu
Xiaofei
X
Gao
Zhixing
Z
Ma
Tianyi
T
CaoSong
Yan-ai
YA
Mei
Yufang
Y
Zheng
D051722:ADAM Proteins / Q000378:metabolism*; D000072197:ADAM10 Protein; D000072198:ADAM17 Protein; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D000818:Animals; D066259:Betacellulin; D019556:COS Cells; D002522:Chlorocebus aethiops; D015870:Gene Expression; D057809:HEK293 Cells; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D021962:Membrane Microdomains / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D017480:Receptors, sigma / Q000819:agonists / Q000378:metabolism*; D000097605:Sigma-1 Receptor
D051722:ADAM Proteins; D000072197:ADAM10 Protein; D000072198:ADAM17 Protein; D053829:Amyloid Precursor Protein Secretases; D066259:Betacellulin; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor; C587851:BTC protein, human; C587883:HBEGF protein, human; C491236:ADAM10 protein, human; C000606462:ADAM17 protein, human