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DOI | 10.1038/s41467-018-05665-9 |
Human adipose glycerol flux is regulated by a pH gate in AQP10 | |
Gotfryd, Kamil1; Mosca, Andreia Filipa2; Missel, Julie Winkel1; Truelsen, Sigurd Friis3; Wang, Kaituo1; Spulber, Mariana4; Krabbe, Simon5; Helix-Nielsen, Claus3,4; Laforenza, Umberto6; Soveral, Graca2; Pedersen, Per Amstrup5; Gourdon, Pontus1,7 | |
2018-11-12 | |
发表期刊 | NATURE COMMUNICATIONS |
ISSN | 2041-1723 |
出版年 | 2018 |
卷号 | 9 |
文章类型 | Article |
语种 | 英语 |
国家 | Denmark; Portugal; Italy; Sweden |
英文摘要 | 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 angstrom 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. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000449763100005 |
WOS关键词 | MOLECULAR-DYNAMICS SIMULATIONS ; X-RAY-STRUCTURE ; CRYSTAL-STRUCTURE ; WATER TRANSPORT ; PLASMA-MEMBRANE ; AQUAPORIN 4 ; CHANNEL ; SELECTIVITY ; ADIPOCYTES ; EXPRESSION |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/203936 |
专题 | 资源环境科学 |
作者单位 | 1.Univ Copenhagen, Dept Biomed Sci, Norre Alle 14, DK-2200 Copenhagen N, Denmark; 2.Univ Lisbon, Res Inst Med iMed ULisboa, Fac Pharm, Av Prof Gama Pinto, P-1649003 Lisbon, Portugal; 3.Tech Univ Denmark, Dept Environm Engn, Bygningstorvet Bldg 115, DK-2800 Lyngby, Denmark; 4.Aquaporin AS, Nymollevej 78, DK-2800 Lyngby, Denmark; 5.Univ Copenhagen, Dept Biol, Univ PK 13, DK-2100 Copenhagen OE, Denmark; 6.Univ Pavia, Dept Mol Med, Human Physiol Unit, Via Forlanini 6, I-27100 Pavia, Italy; 7.Lund Univ, Dept Expt Med Sci, Solvegatan 19, SE-221 Lund, Sweden |
推荐引用方式 GB/T 7714 | Gotfryd, Kamil,Mosca, Andreia Filipa,Missel, Julie Winkel,et al. Human adipose glycerol flux is regulated by a pH gate in AQP10[J]. NATURE COMMUNICATIONS,2018,9. |
APA | Gotfryd, Kamil.,Mosca, Andreia Filipa.,Missel, Julie Winkel.,Truelsen, Sigurd Friis.,Wang, Kaituo.,...&Gourdon, Pontus.(2018).Human adipose glycerol flux is regulated by a pH gate in AQP10.NATURE COMMUNICATIONS,9. |
MLA | Gotfryd, Kamil,et al."Human adipose glycerol flux is regulated by a pH gate in AQP10".NATURE COMMUNICATIONS 9(2018). |
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