Sigma1 receptors inhibit store-operated Ca2+entry by attenuating coupling of STIM1 to Orai1

Srivats, Shyam, Balasuriya, Dilshan, Pasche, Mathias, Vistal, Gerard, Edwardson, J Michael, Taylor, Colin W and Murrell-Lagnado, Ruth D (2016) Sigma1 receptors inhibit store-operated Ca2+entry by attenuating coupling of STIM1 to Orai1. The Journal of Cell Biology, 213 (1). pp. 65-79. ISSN 0021-9525

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Abstract

Sigma1 receptors (σ1Rs) are expressed widely; they bind diverse ligands, including psychotropic drugs and steroids, regulate many ion channels, and are implicated in cancer and addiction. It is not known how σ1Rs exert such varied effects. We demonstrate that σ1Rs inhibit store-operated Ca2+ entry (SOCE), a major Ca2+ influx pathway, and reduce the Ca2+ content of the intracellular stores. SOCE was inhibited by expression of σ1R or an agonist of σ1R, and enhanced by loss of σ1R or an antagonist. Within the endoplasmic reticulum (ER), σ1R associated with STIM1, the ER Ca2+-sensor that regulates SOCE. This interaction was modulated by σ1R ligands. After depletion of Ca2+ stores, σ1R accompanied STIM1 to ER-plasma membrane (PM) junctions where STIM1 stimulated opening of the Ca2+ channel, Orai1. The association of STIM1 with σ1R slowed the recruitment of STIM1 to ER-PM junctions and reduced binding of STIM1 to PM Orai1. We conclude that σ1R attenuates STIM1 coupling to Orai1, and thereby inhibits SOCE.

Item Type: Article
Schools and Departments: School of Life Sciences > Neuroscience
Subjects: Q Science > QP Physiology > QP0351 Neurophysiology and neuropsychology
Depositing User: Ruth Murrell-Lagnado
Date Deposited: 27 Apr 2016 08:54
Last Modified: 07 Mar 2017 12:06
URI: http://sro.sussex.ac.uk/id/eprint/60627

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