Mom, R.; Réty, S.; Auguin, D. Cortisol Interaction with Aquaporin-2 Modulates Its Water Permeability: Perspectives for Non-Genomic Effects of Corticosteroids. Int. J. Mol. Sci.2023, 24, 1499.
Mom, R.; Réty, S.; Auguin, D. Cortisol Interaction with Aquaporin-2 Modulates Its Water Permeability: Perspectives for Non-Genomic Effects of Corticosteroids. Int. J. Mol. Sci. 2023, 24, 1499.
Mom, R.; Réty, S.; Auguin, D. Cortisol Interaction with Aquaporin-2 Modulates Its Water Permeability: Perspectives for Non-Genomic Effects of Corticosteroids. Int. J. Mol. Sci.2023, 24, 1499.
Mom, R.; Réty, S.; Auguin, D. Cortisol Interaction with Aquaporin-2 Modulates Its Water Permeability: Perspectives for Non-Genomic Effects of Corticosteroids. Int. J. Mol. Sci. 2023, 24, 1499.
Abstract
Aquaporins (AQPs) are water channels widely distributed in living organisms and involved in many pathophysiologies as well as in cell volume regulations (CVR). In the present study, based on the structural homology existing between mineralocorticoids receptors (MR), glucocorticoids receptors (GR), cholesterol consensus motif (CCM) and the extra-cellular vestibules of AQPs, we investigated the binding of corticosteroids on AQP family through in silico molecular dynamics simulations of AQP2 interactions with cortisol. We propose for the first time a putative AQPs corticosteroids binding site (ACBS) and discussed its conservation through structural alignment. Corticosteroids can mediate non-genomic effects, nonetheless, the transduction pathways involved are still misunderstood. Moreover, a growing body of evidence is pointing out toward the existence of a novel membrane receptor mediating part of these rapid corticosteroids effects. Our results suggest that the naturally produced glucocorticoid cortisol inhibits channel water permeability. Based on these results, we propose a detailed description of a putative underlying molecular mechanism. In this process, we also bring new insights on the regulatory function of AQPs extra-cellular loops and on the role of ions in tuning the water permeability. Altogether, this work brings new insights into corticosteroids non-genomic effects through the proposition of AQPs as membrane receptor of this family of regulatory molecules. This original result is the starting point for future investigations to define more in depth and in vivo the validity of this functional model.
Keywords
AQP2; cortisol; corticosteroid; non-genomic effects; molecular dynamics; water permeability
Subject
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
