The Sigma-1 Receptor in Cellular Stress Signaling

Frontiers in Neuroscience
Teruo Hayashi

Abstract

After decades of research, the sigma-1 receptor (Sig-1R)'s structure, and molecular functions are being unveiled. Sig-1R is an integral endoplasmic reticulum (ER) membrane protein which forms an oligomer and binds a variety of psychotropic drugs. It forms a complex with the ER chaperone BiP that controls specific signaling molecules' stability and function at the ER to regulate Ca2+ signaling, bioenergetics, and ER stress. Sig-1R is highly enriched in ER subdomains that are physically linked to outer mitochondrial membranes, reflecting its role in regulating ER-mitochondria communications. Thus, Sig-1R ligands are expected to serve as novel neuroprotective agents which treat certain psychiatric and neurodegenerative disorders. In this short review, the cell biological aspects of Sig-1R are discussed, with a particular focus on its role in fundamental ER functions.

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Citations

Jun 11, 2020·International Journal of Molecular Sciences·Nikoletta AlmásiKrisztina Kupai
Oct 1, 2020·International Journal of Molecular Sciences·Mikhail V VoroninSergei B Seredenin
Jul 20, 2020·Neurobiology of Disease·Dawn H W LauChristopher C J Miller
Jan 28, 2021·Genes·Ilaria Pontisso, Laurent Combettes
Dec 29, 2020·Frontiers in Pharmacology·José Miguel Vela
Apr 10, 2020·Progress in Retinal and Eye Research·Marina S GorbatyukOleg S Gorbatyuk
Mar 16, 2021·Experimental Biology and Medicine·Mengting KeYancheng Xu
May 1, 2021·International Journal of Molecular Sciences·Vladimir ZhemkovIlya Bezprozvanny
Aug 8, 2021·International Journal of Molecular Sciences·Szabolcs DvorácskóFerenc Bogár
Nov 25, 2021·Journal of Neurochemistry·Hannah N Saeger, David E Olson

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Methods Mentioned

BETA
FRET
NMR
light-scattering
BRET
electrophoresis

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