Human adipose glycerol flux is regulated by a pH gate in AQP10
| Autor: | Umberto Laforenza, Kamil Gotfryd, Julie Winkel Missel, Claus Hélix-Nielsen, Pontus Gourdon, Andreia F. Mósca, Per Amstrup Pedersen, Kaituo Wang, Mariana Spulber, Sigurd Friis Truelsen, Graça Soveral, Simon Krabbe |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Glycerol Male Science General Physics and Astronomy Adipose tissue Aquaporin Molecular Dynamics Simulation Aquaporins 01 natural sciences General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences chemistry.chemical_compound SDG 3 - Good Health and Well-being In vivo 0103 physical sciences Adipocytes Lipolysis Humans Secretion lcsh:Science Aged Principal Component Analysis Multidisciplinary 010304 chemical physics Chemistry General Chemistry Hydrogen-Ion Concentration Middle Aged 030104 developmental biology Adipose Tissue Biophysics lcsh:Q Female Flux (metabolism) Ion Channel Gating Homeostasis |
| Zdroj: | Nature Communications Gotfryd, K, Mósca, A F, Missel, J W, Truelsen, S F, Wang, K, Spulber, M, Krabbe, S, Hélix-nielsen, C, Laforenza, U, Soveral, G, Pedersen, P A & Gourdon, P E 2018, ' Human adipose glycerol flux is regulated by a pH gate in AQP10 ', Nature Communications, vol. 9, 4749, pp. 1-11 . https://doi.org/10.1038/s41467-018-07176-z Nature Communications, Vol 9, Iss 1, Pp 1-11 (2018) Gotfryd, K, Mósca, A F, Missel, J W, Truelsen, S F, Wang, K, Spulber, M, Krabbe, S, Hélix-Nielsen, C, Laforenza, U, Soveral, G, Pedersen, P A & Gourdon, P 2018, ' Human adipose glycerol flux is regulated by a pH gate in AQP10 ', Nature Communications, vol. 9, no. 1, 4749 . https://doi.org/10.1038/s41467-018-07176-z |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-018-07176-z |
| Popis: | Obesity is a major threat to global health and metabolically associated with glycerol homeostasis. Here we demonstrate that in human adipocytes, the decreased pH observed during lipolysis (fat burning) correlates with increased glycerol release and stimulation of aquaglyceroporin AQP10. The crystal structure of human AQP10 determined at 2.3 Å resolution unveils the molecular basis for pH modulation—an exceptionally wide selectivity (ar/R) filter and a unique cytoplasmic gate. Structural and functional (in vitro and in vivo) analyses disclose a glycerol-specific pH-dependence and pinpoint pore-lining His80 as the pH-sensor. Molecular dynamics simulations indicate how gate opening is achieved. These findings unravel a unique type of aquaporin regulation important for controlling body fat mass. Thus, targeting the cytoplasmic gate to induce constitutive glycerol secretion may offer an attractive option for treating obesity and related complications. Uptake and release of glycerol from the small intestine and adipocytes is facilitated by a subclass of aquaporins (AQP), but how glycerol flow is regulated remains poorly understood. Here authors solve the crystal structure of AQP10 and show how lipolysis is coupled to AQP10 regulation in |
| Databáze: | OpenAIRE |
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