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. 2012 Feb 9;3(2):153–159. doi: 10.1007/s13238-012-2006-9

Overexpression of sigma-1 receptor inhibits ADAM10 and ADAM17 mediated shedding in vitro

Juan Li 1, Bin Liu 1, Xiaofei Gao 1, Zhixing Ma 1, Tianyi CaoSong 1, Yan-ai Mei 1, Yufang Zheng 1,✉
PMCID: PMC4875409  PMID: 22322890

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.

Keywords: sigma-1 receptor, ADAM17, ADAM10, shedding, lipid raft

Footnotes

An erratum to this article can be found at http://dx.doi.org/10.1007/s13238-012-2805-z.

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