Journal
FRONTIERS IN NEUROSCIENCE
Volume 13, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fnins.2019.01186
Keywords
sigma-1 receptor; chaperone protein; voltage-gated ion channels; intrinsic excitability; plasticity; nervous system disorders; cancer; drug addiction
Categories
Funding
- Fondation ARC [PJA20161204740, PJA20181207701]
- Fondation de France [FdF Eotp 535412]
- Canceropole PACA
- National Institutes of Health (National Institute on Drug Abuse) [R01DA041390]
- Universite du Quebec a Montreal (UQAM)
- Natural Sciences and Engineering Research Council of Canada (NSERC) [RGPIN-2019-06666]
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The sigma-1 receptor (sigma 1R) is an endoplasmic reticulum (ER)-resident chaperone protein that acts like an inter-organelle signaling modulator. Among its several functions such as ER lipid metabolisms/transports and indirect regulation of genes transcription, one of its most intriguing feature is the ability to regulate the function and trafficking of a variety of functional proteins. To date, and directly relevant to the present review, sigma 1R has been found to regulate both voltage-gated ion channels (VGICs) belonging to distinct superfamilies (i.e., sodium, Na+; potassium, K+; and calcium, Ca2+ channels) and non-voltage-gated ion channels. This regulatory function endows sigma 1R with a powerful capability to fine tune cells' electrical activity and calcium homeostasis-a regulatory power that appears to favor cell survival in pathological contexts such as stroke or neurodegenerative diseases. In this review, we present the current state of knowledge on sigma 1R's role in the regulation of cellular electrical activity, and how this seemingly adaptive function can shift cell homeostasis and contribute to the development of very distinct chronic pathologies such as psychostimulant abuse and tumor cell growth in cancers.
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