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Front. Neurosci. | doi: 10.3389/fnins.2019.00733

The sigma-1 receptor in cellular stress signaling

  • 1Nishikawa Hospital, Japan

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.

Keywords: sigma-1 receptor, Endoplasmic Reticulum, er stress, Ca2+, Oxidative Stress

Received: 28 Apr 2019; Accepted: 01 Jul 2019.

Edited by:

Saïd Kourrich, Université du Québec à Montréal, Canada

Reviewed by:

Kenji Hashimoto, Chiba University, Japan
Arnold E. Ruoho, University of Wisconsin School of Medicine and Public Health, United States  

Copyright: © 2019 Hayashi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Mx. Teruo Hayashi, Nishikawa Hospital, Hamada, Japan,