| Title: |
Cortisol Interaction with Aquaporin-2 Modulates Its Water Permeability: Perspectives for Non-Genomic Effects of Corticosteroids |
| Authors: |
Mom, Robin; Réty, Stéphane; Auguin, Daniel |
| Contributors: |
Laboratoire de biologie et modélisation de la cellule (LBMC UMR 5239); École normale supérieure de Lyon (ENS de Lyon); Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL); Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| Source: |
ISSN: 1661-6596. |
| Publisher Information: |
CCSD; MDPI |
| Publication Year: |
2023 |
| Collection: |
HAL Lyon 1 (University Claude Bernard Lyon 1) |
| Subject Terms: |
Réty; Auguin; D. Cortisol Interaction with Aquaporin-2 Modulates Its Water Permeability: Perspectives for Non-Genomic Effects of AQP2; cortisol; corticosteroid; non-genomic effects; molecular dynamics; water permeability; D. Cortisol Interaction with Aquaporin-2 Modulates Its Water Permeability: Perspectives for Non-Genomic Effects of AQP2 cortisol corticosteroid non-genomic effects molecular dynamics water permeability; S. Auguin; R. Réty; Mom; [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry; Molecular Biology/Structural Biology [q-bio.BM] |
| Description: |
International audience ; 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 mineralocorticoid receptors (MRs), glucocorticoid receptors (GRs), cholesterol consensus motif (CCM) and the extra-cellular vestibules of AQPs, we investigated the binding of corticosteroids on the AQP family through in silico molecular dynamics simulations of AQP2 interactions with cortisol. We propose, for the first time, a putative AQPs corticosteroid 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 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 the non-genomic effects of corticosteroids through the proposition of AQPs as the 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.3390/ijms24021499 |
| Availability: |
https://hal.science/hal-04019840; https://hal.science/hal-04019840v1/document; https://hal.science/hal-04019840v1/file/ijms-24-01499-v2.pdf; https://doi.org/10.3390/ijms24021499 |
| Rights: |
https://about.hal.science/hal-authorisation-v1/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.104C4F79 |
| Database: |
BASE |