Sigma1 receptors inhibit store-operated Ca<sup>2+</sup> entry by attenuating coupling of STIM1 to Orai1

Srivats, Shyam; Balasuriya, Dilshan; Pasche, Mathias; Vistal, Gerard; Edwardson, J. Michael; Taylor, Colin W.; Murrell‐Lagnado, Ruth D.

doi:10.1085/jgp.1475oia26

Cited by 5 publications

(7 citation statements)

References 16 publications

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“…organelles such as mitochondria and the plasma membrane. This hypothesis is consistent with the fact that S1R is enriched in MCS between ER and mitochondria (Hayashi and Su, 2007;Zhemkov et al, 2021a), ER-PM junctions (Srivats et al, 2016;Zhemkov et al, 2021a) and ER-lipid droplets (Hayashi and Su, 2003). We further propose that the physical properties of these S1R domains, such as their high cholesterol content, higher rigidity and flat geometry can facilitate the initial formation of stable contacts between the ER membrane and membranes of other organelles.…”

Section: Discussionsupporting

confidence: 89%

Sigma 1 Receptor, Cholesterol and Endoplasmic Reticulum Contact Sites

Zhemkov

Liou

Bezprozvanny

2021

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Recent studies indicated potential importance of membrane contact sites (MCS) between the endoplasmic reticulum (ER) and other cellular organelles. These MCS have unique protein and lipid composition and serve as hubs for inter-organelle communication and signaling. Despite extensive investigation of MCS protein composition and functional roles, little is known about the process of MCS formation. In this perspective, we propose a hypothesis that MCS are formed not as a result of random interactions between membranes of ER and other organelles but on the basis of pre-existing cholesterol-enriched ER microdomains.

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Section: Discussionsupporting

confidence: 89%

Sigma 1 Receptor, Cholesterol and Endoplasmic Reticulum Contact Sites

Zhemkov

Liou

Bezprozvanny

2021

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“…Calcium influx via the STIM1/Orai complex is one mechanism by which the cardiac action potential is altered in the hypertrophic heart; inhibition of this calcium entry pathway has been shown to improve cardiac function [55]. Sigma-1R provides a novel method for inhibition of this pathway, as it’s activation also inhibits store-operated calcium entry [56].…”

Section: Sigma-1r Modulation Of Cardiac Ion Channelsmentioning

confidence: 95%

Is the sigma-1 receptor a potential pharmacological target for cardiac pathologies? A systematic review

Lewis

McCormick

et al. 2020

IJC Heart & Vasculature

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Sigma-1 receptors are ligand-regulated chaperone proteins, involved in several cellular mechanisms. The aim of this systematic review was to examine the effects that the sigma-1 receptor has on the cardiovascular system. The interaction targets and proposed mechanisms of action of sigma-1 receptors were explored, with the aim of determining if the sigma-1 receptor is a potential pharmacological target for cardiac pathologies. This systematic review was conducted according to the PRISMA guidelines and these were used to critically appraise eligible studies. Pubmed and Scopus were systematically searched for articles investigating sigma-1 receptors in the cardiovascular system. Papers identified by the search terms were then subject to analysis against pre-determined inclusion criteria. 23 manuscripts met the inclusion criteria and were included in this review. The experimental platforms, experimental techniques utilised and the results of the studies were summarised. The sigma-1 receptor is found to be implicated in cardioprotection, via various mechanisms including stimulating the Akt-eNOS pathway, and reduction of Ca2 + leakage into the cytosol via modulating certain calcium channels. Sigma-1 receptors are also found to modulate other cardiac ion channels including different subtypes of potassium and sodium channels and have been shown to modulate intracardiac neuron excitability. The sigma-1 receptor is a potential therapeutic target for treatment of cardiac pathologies, particularly cardiac hypertrophy. We therefore suggest investigating the cardioprotective mechanisms of sigma-1 receptor function, alongside proposed potential ligands that can stimulate these functions.

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“…Sigmar1 resides at mitochondria-associated ER membrane, inhibiting store-operated calcium entry. 60 Inhibition of Sigmar1 was reported to attenuate cognitive deficits in an AD mouse model with intraventricle Aβ injection. 61 In our cultured neurons, deletion of p38α-MAPK enhances both glutamate-triggered calcium influx and the clearance of cytoplasmic calcium after glutamate removal.…”

Section: F I G U R Ementioning

confidence: 99%

Neuronal deficiency of p38α‐MAPK ameliorates symptoms and pathology of APP or Tau‐transgenic Alzheimer’s mouse models

et al. 2020

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

Cited by 5 publications

References 16 publications

Sigma 1 Receptor, Cholesterol and Endoplasmic Reticulum Contact Sites

Sigma 1 Receptor, Cholesterol and Endoplasmic Reticulum Contact Sites

Is the sigma-1 receptor a potential pharmacological target for cardiac pathologies? A systematic review

Neuronal deficiency of p38α‐MAPK ameliorates symptoms and pathology of APP or Tau‐transgenic Alzheimer’s mouse models

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

Cited by 5 publications

References 16 publications

Sigma 1 Receptor, Cholesterol and Endoplasmic Reticulum Contact Sites

Sigma 1 Receptor, Cholesterol and Endoplasmic Reticulum Contact Sites

Is the sigma-1 receptor a potential pharmacological target for cardiac pathologies? A systematic review

Neuronal deficiency of p38α‐MAPK ameliorates symptoms and pathology of APP or Tau‐transgenic Alzheimer’s mouse models

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Product

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