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Karst H, den Boon FS, Vervoort N, et al. Non-genomic steroid signaling through the mineralocorticoid receptor: Involvement of a membrane-associated receptor?. Mol Cell Endocrinol. 2021;541:111501doi: 10.1016/j.mce.2021.111501.
Karst, H., den Boon, F. S., Vervoort, N., Adrian, M., Kapitein, L. C., & Joëls, M. (2021). Non-genomic steroid signaling through the mineralocorticoid receptor: Involvement of a membrane-associated receptor?. Molecular and cellular endocrinology, 541111501. https://doi.org/10.1016/j.mce.2021.111501
Karst, Henk, et al. "Non-genomic steroid signaling through the mineralocorticoid receptor: Involvement of a membrane-associated receptor?." Molecular and cellular endocrinology vol. 541 (2021): 111501. doi: https://doi.org/10.1016/j.mce.2021.111501
Karst H, den Boon FS, Vervoort N, Adrian M, Kapitein LC, Joëls M. Non-genomic steroid signaling through the mineralocorticoid receptor: Involvement of a membrane-associated receptor?. Mol Cell Endocrinol. 2021 Nov 02;541:111501. doi: 10.1016/j.mce.2021.111501. Epub 2021 Nov 02. PMID: 34740745.
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Mol Cell Endocrinol. 2021 Nov 02;541:111501. doi: 10.1016/j.mce.2021.111501. Epub 2021 Nov 02.

Non-genomic steroid signaling through the mineralocorticoid receptor: Involvement of a membrane-associated receptor?.

Molecular and cellular endocrinology

Henk Karst, Femke S den Boon, Niek Vervoort, Max Adrian, Lukas C Kapitein, Marian Joëls

Affiliations

  1. Dept Translational Neuroscience, University Medical Center Utrecht, Utrecht University, the Netherlands. Electronic address: [email protected].
  2. Dept Translational Neuroscience, University Medical Center Utrecht, Utrecht University, the Netherlands.
  3. University Utrecht, Faculty of Science, Division of Cell Biology, Utrecht, the Netherlands.
  4. Dept Translational Neuroscience, University Medical Center Utrecht, Utrecht University, the Netherlands; University Medical Center Groningen, University of Groningen, the Netherlands.

PMID: 34740745 DOI: 10.1016/j.mce.2021.111501

Abstract

Corticosteroid receptors in the mammalian brain mediate genomic as well as non-genomic actions. Although receptors mediating genomic actions were already cloned 35 years ago, it remains unclear whether the same molecules are responsible for the non-genomic actions or that the latter involve a separate class of receptors. Here we focus on one type of corticosteroid receptors, i.e. the mineralocorticoid receptor (MR). We summarize some of the known properties and the current insight in the localization of the MR in peripheral cells and neurons, especially in relation to non-genomic signaling. Previous studies from our own and other labs provided evidence that MRs mediating non-genomic actions are identical to the ones involved in genomic signaling, but may be translocated to the plasma cell membrane instead of the nucleus. With fixed cell imaging and live cell imaging techniques we tried to visualize these presumed membrane-associated MRs, using antibodies or overexpression of MR-GFP in COS7 and hippocampal cultured neurons. Despite the physiological evidence for MR location in or close to the cell membrane, we could not convincingly visualize membrane localization of endogenous MRs or GFP-MR molecules. However, we did find punctae of labeled antibodies intracellularly, which might indicate transactivating spots of MR near the membrane. We also found some evidence for trafficking of MR via beta-arrestins. In beta-arrestin knockout mice, we didn't observe metaplasticity in the basolateral amygdala anymore, indicating that internalization of MRs could play a role during corticosterone activation. Furthermore, we speculate that membrane-associated MRs could act indirectly via activating other membrane located structures like e.g. GPER and/or receptor tyrosine kinases.

Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.

Keywords: Beta-arrestin; Internalization; Membrane localization; Mineralocorticoid receptor; Non-genomic

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