Molecular Interplay Between the Sigma-1 Receptor, Steroids, and Ion Channels

Morales‐Lázaro, Sara L.; González‐Ramírez, Ricardo; Rosenbaum, Tamara

doi:10.3389/fphar.2019.00419

Cited by 45 publications

(29 citation statements)

References 84 publications

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“…This suggests that Sig1R is not limited to chaperoning specific substrates, but also has a homeostasis-maintaining role for the ER. This role is apparently lost upon prolonged ER stress of more than 30 mins or upon agonist binding, when Sig1R relocates from MERCs to other domains of the ER and the plasma membrane, where it interacts with ion channels [43]. These interactions frequently result in the inactivation of K + [44] and Ca 2+ channels [45].…”

Section: Sigma-1 Receptor (Sig1r) Controls a Subset Of Contact Sitmentioning

confidence: 99%

Mechanistic Connections between Endoplasmic Reticulum (ER) Redox Control and Mitochondrial Metabolism

Fan

Simmen

2019

Cells

109

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The past decade has seen the emergence of endoplasmic reticulum (ER) chaperones as key determinants of contact formation between mitochondria and the ER on the mitochondria-associated membrane (MAM). Despite the known roles of ER–mitochondria tethering factors like PACS-2 and mitofusin-2, it is not yet entirely clear how they mechanistically interact with the ER environment to determine mitochondrial metabolism. In this article, we review the mechanisms used to communicate ER redox and folding conditions to the mitochondria, presumably with the goal of controlling mitochondrial metabolism at the Krebs cycle and at the electron transport chain, leading to oxidative phosphorylation (OXPHOS). To achieve this goal, redox nanodomains in the ER and the interorganellar cleft influence the activities of ER chaperones and Ca2+-handling proteins to signal to mitochondria. This mechanism, based on ER chaperones like calnexin and ER oxidoreductases like Ero1α, controls reactive oxygen production within the ER, which can chemically modify the proteins controlling ER–mitochondria tethering, or mitochondrial membrane dynamics. It can also lead to the expression of apoptotic or metabolic transcription factors. The link between mitochondrial metabolism and ER homeostasis is evident from the specific functions of mitochondria–ER contact site (MERC)-localized Ire1 and PERK. These functions allow these two transmembrane proteins to act as mitochondria-preserving guardians, a function that is apparently unrelated to their functions in the unfolded protein response (UPR). In scenarios where ER stress cannot be resolved via the activation of mitochondrial OXPHOS, MAM-localized autophagosome formation acts to remove defective portions of the ER. ER chaperones such as calnexin are again critical regulators of this MERC readout.

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Section: Sigma-1 Receptor (Sig1r) Controls a Subset Of Contact Sitmentioning

confidence: 99%

Mechanistic Connections between Endoplasmic Reticulum (ER) Redox Control and Mitochondrial Metabolism

Fan

Simmen

2019

Cells

109

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“…Upon agonist binding Sig-1R translocates at the plasma membrane where it interacts with ion channels [50][51][52][53]. Many factors among which steroids act on the Sig-1R resulting in negative or positive effects on the function and plasma membrane expression of potassium, calcium, and TRP channels [54]. Sig-1R was described to interact with TRPV1, TRPA1, TRPM8 in calcium and ligand-dependent ways [55,56].…”

Section: Trp Channel Interactorsmentioning

confidence: 99%

Partners in Crime: Towards New Ways of Targeting Calcium Channels

Noyer

Lemonnier

Mariot

et al. 2019

IJMS

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The characterization of calcium channel interactome in the last decades opened a new way of perceiving ion channel function and regulation. Partner proteins of ion channels can now be considered as major components of the calcium homeostatic mechanisms, while the reinforcement or disruption of their interaction with the channel units now represents an attractive target in research and therapeutics. In this review we will focus on the targeting of calcium channel partner proteins in order to act on the channel activity, and on its consequences for cell and organism physiology. Given the recent advances in the partner proteins’ identification, characterization, as well as in the resolution of their interaction domain structures, we will develop the latest findings on the interacting proteins of the following channels: voltage-dependent calcium channels, transient receptor potential and ORAI channels, and inositol 1,4,5-trisphosphate receptor.

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“…There is a myriad of genes transcriptionally regulated by SH, including a number of ion channels (Kim et al, 2006;Lee and Jeung, 2007;Fraser et al, 2014). Something really fascinating is that SH may also regulate the activity of ion channels by acting on its gating properties, either by inducing the expression of ion channel-interacting proteins, or by direct binding to channels (Majewska et al, 1986;Valverde et al, 1999;Herd et al, 2007;Strünker et al, 2011;Kow and Pfaff, 2016;Morales-Lázaro et al, 2019). The effect of SH on ion channels seems to be a relevant mechanism by which steroids meet many of their physiological functions in both, the cardiovascular and nervous systems, as well as in non-excitable tissues.…”

Section: Steroid Hormones Regulate the Expression And/or Activity Of mentioning

confidence: 99%

Ion Channel Regulation by Sex Steroid Hormones and Vitamin D in Cancer: A Potential Opportunity for Cancer Diagnosis and Therapy

2020

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Many ion channels are involved in tumor development, promoting cancer cell proliferation, migration, invasion, and survival. Accordingly, some of them have been suggested as tumor markers and novel targets for cancer therapy. Some sex steroid hormones (SSH), including estrogens and androgens, favor cancer progression. Meanwhile, other steroid hormones like vitamin D may have anticancer properties. SSH and vitamin D modulate the expression of a number of ion channels in cancer cells from hormone-sensitive tissues, including breast, ovary, prostate, and cervix. Moreover, rapid effects of SSH may be mediated by their direct action on membrane ion channels. Here, we reviewed the SSH and vitamin D regulation of ion channels involved in cancer, and analyzed the potential molecular pathways implicated. In addition, we described the potential clinical use of ion channels in cancer diagnosis and therapy, taking advantage of their regulation by SSH and vitamin D. Since SSH are considered risk factors for different types of cancer, and ion channels play important roles in tumor progression, the regulation of ion channels by SSH and vitamin D may represent a potential opportunity for early cancer diagnosis and therapeutic approaches in SSH and vitamin D sensitive tumors.

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Molecular Interplay Between the Sigma-1 Receptor, Steroids, and Ion Channels

Cited by 45 publications

References 84 publications

Mechanistic Connections between Endoplasmic Reticulum (ER) Redox Control and Mitochondrial Metabolism

Mechanistic Connections between Endoplasmic Reticulum (ER) Redox Control and Mitochondrial Metabolism

Partners in Crime: Towards New Ways of Targeting Calcium Channels

Ion Channel Regulation by Sex Steroid Hormones and Vitamin D in Cancer: A Potential Opportunity for Cancer Diagnosis and Therapy

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