title: Oestrogen-related receptor α is required for transepithelial H+ secretion in zebrafish.
abstract: Oestrogen-related receptor α (ERRα) is an orphan nuclear receptor which is important for adaptive metabolic responses under conditions of increased energy demand, such as cold, exercise and fasting. Importantly, metabolism under these conditions is usually accompanied by elevated production of organic acids, which may threaten the body acid-base status. Although ERRα is known to help regulate ion transport by the renal epithelia, its role in the transport of acid-base equivalents remains unknown. Here, we tested the hypothesis that ERRα is involved in acid-base regulation mechanisms by using zebrafish as the model to examine the effects of ERRα on transepithelial H(+) secretion. ERRα is abundantly expressed in H(+)-pump-rich cells (HR cells), a group of ionocytes responsible for H(+) secretion in the skin of developing embryos, and its expression is stimulated by acidic (pH 4) environments. Knockdown of ERRα impairs both basal and low pH-induced H(+) secretion in the yolk-sac skin, which is accompanied by decreased expression of H(+)-secreting-related transporters. The effect of ERRα on H(+) secretion is achieved through regulating both the total number of HR cells and the function of individual HR cells. These results demonstrate, for the first time, that ERRα is required for transepithelial H(+) secretion for systemic acid-base homeostasis.
authors.affiliation: Institute of Biological Chemistry, Academia Sinica, Taipei 11529, Taiwan, Republic of China Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 11529, Taiwan, Republic of China.
authors.forename: Ying-Jey
authors.initials: YJ
authors.lastname: Guh
authors.affiliation: Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 11529, Taiwan, Republic of China.
authors.forename: Chao-Yew
authors.initials: CY
authors.lastname: Yang
authors.affiliation: Department of Life Science, National Taiwan Normal University, Taipei 11677, Taiwan, Republic of China.
authors.forename: Sian-Tai
authors.initials: ST
authors.lastname: Liu
authors.affiliation: Institute of Biological Chemistry, Academia Sinica, Taipei 11529, Taiwan, Republic of China.
authors.forename: Chang-Jen
authors.initials: CJ
authors.lastname: Huang
authors.affiliation: Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 11529, Taiwan, Republic of China pphwang@gate.sinica.edu.tw.
authors.forename: Pung-Pung
authors.identifier: http://orcid.org/0000-0002-5534-2812
authors.initials: PP
authors.lastname: Hwang
mesh_terms: D000818:Animals; D004734:Energy Metabolism; D004847:Epithelial Cells / Q000502:physiology; D006859:Hydrogen / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000235:genetics* / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D000097983:ERRalpha Estrogen-Related Receptor
chemical_list: D006859:Hydrogen; D011960:Receptors, Estrogen; D000097983:ERRalpha Estrogen-Related Receptor
keywords: H+ secretion; H+-ATPase-rich cell; oestrogen-related receptor α; zebrafish