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

Juan Li; Bin Liu; Xiaofei Gao; Zhixing Ma; Tianyi CaoSong; Yan ai Mei; Yufang Zheng

doi:10.1007/s13238-012-2006-9

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

Juan Li, Bin Liu, Xiaofei Gao, Zhixing Ma, Tianyi CaoSong, Yan ai Mei, Yufang Zheng

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

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.

Original language	English (US)
Pages (from-to)	153-159
Number of pages	7
Journal	Protein and Cell
Volume	3
Issue number	2
DOIs	https://doi.org/10.1007/s13238-012-2006-9
State	Published - Feb 2012
Externally published	Yes

Keywords

ADAM10
ADAM17
lipid raft
shedding
sigma-1 receptor

ASJC Scopus subject areas

Biotechnology
Biochemistry
Drug Discovery
Cell Biology

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10.1007/s13238-012-2006-9

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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.",

keywords = "ADAM10, ADAM17, lipid raft, shedding, sigma-1 receptor",

author = "Juan Li and Bin Liu and Xiaofei Gao and Zhixing Ma and Tianyi CaoSong and Mei, {Yan ai} and Yufang Zheng",

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AU - Li, Juan

AU - Liu, Bin

AU - Gao, Xiaofei

AU - Ma, Zhixing

AU - CaoSong, Tianyi

AU - Mei, Yan ai

AU - Zheng, Yufang

PY - 2012/2

Y1 - 2012/2

N2 - 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.

AB - 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.

KW - ADAM10

KW - ADAM17

KW - lipid raft

KW - shedding

KW - sigma-1 receptor

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

Abstract

Keywords

ASJC Scopus subject areas

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