Overexpression of sigma-1 receptor inhibits ADAM10 and ADAM17 mediated shedding in vitro |
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Authors: | Juan Li Bin Liu Xiaofei Gao Zhixing Ma Tianyi CaoSong Yan-ai Mei Yufang Zheng |
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Affiliation: | School of Life Sciences, Fudan University, Shanghai 200433, China |
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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. |
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Keywords: | sigma-1 receptor ADAM17 ADAM10 shedding lipid raft |
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