Oestrogen-related receptor α is required for transepithelial H ⁺ secretion in zebrafish

Abstract

Oestrogen-related receptor a (ERRa) 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 ERRa 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 ERRa is involved in acid-base regulation mechanisms by using zebrafish as the model to examine the effects of ERRa on transepithelial H þ secretion. ERRa is abundantly expressed in H þ -pump-rich cells (HR cells), a group of ionocytes responsible for H þ secretion in the skin of developing embryos, and its expression is stimulated by acidic (pH 4) environments. Knockdown of ERRa impairs both basal and low pH-induced H þ secretion in the yolk-sac skin, which is accompanied by decreased expression of H þ -secreting-related transporters. The effect of ERRa on H þ 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 ERRa is required for transepithelial H þ secretion for systemic acid-base homeostasis.

Zebrafish as a Model System for Investigating the Compensatory Regulation of Ionic Balance during Metabolic Acidosis

“…In zebrafish, several neuroendocrine factors are found to be involved in ionic and acid-base regulation during acid exposure, including cortisol [ 38 , 83 ], endothelin 1 [ 103 ], angiotensin II [ 104 ], stanniocalcin [ 49 , 105 ], catecholamines [ 106 ] and oestrogen-related receptor [ 107 ]. In other FW fish species, mRNA expression and/or plasma levels of thyroid hormone [ 108 ], prolactin [ 109 ], growth hormone [ 110 ] and somatolactin [ 110 , 111 ] are found to be modulated by acid exposure.…”

“…The oestrogen-related receptor (ERR) belongs to orphan nuclear receptors which control the transcription of several genes essential in energy metabolism in mammals [ 125 ]. In zebrafish, it was recently demonstrated that ERRa is involved in promoting acid secretion in zebrafish, partially by increasing the density of HRCs [ 107 ]. erra mRNA was found to be expressed in HRCs, and that acid exposure increased its abundance [ 107 ].…”

“…In zebrafish, it was recently demonstrated that ERRa is involved in promoting acid secretion in zebrafish, partially by increasing the density of HRCs [ 107 ]. erra mRNA was found to be expressed in HRCs, and that acid exposure increased its abundance [ 107 ]. ERRa was also demonstrated to positively regulate the mRNA expressions of nhe3b , atp6v1a (encodes for H + -ATPase) and ae1b [ 107 ].…”

“…erra mRNA was found to be expressed in HRCs, and that acid exposure increased its abundance [ 107 ]. ERRa was also demonstrated to positively regulate the mRNA expressions of nhe3b , atp6v1a (encodes for H + -ATPase) and ae1b [ 107 ]. This is a novel finding on the role of ERRa in acid-base regulation in vertebrates.…”

Measuring Extracellular Proton and Anionic Fluxes in Arabidopsis Pollen Tubes

“…Ideally, any biological system of interest should be studied with the minimum interference and under the most physiological condition possible. Such criteria are attained by the non-invasive ion-selective vibrating probe, which has been used for measuring multiple transmembrane ion fluxes in a wide variety of experimental systems, including Drosophila (Browne and O'Donnell, 2016), zebrafish (Guh et al, 2016), mouse skin (Sun et al, 2015), roots (He et al, 2015), Daphnia (Stensberg et al, 2014), C. elegans (Adlimoghaddam et al, 2014), etc. In pollen tubes, quantitative measurements of extracellular ion fluxes using the ion-selective vibrating probe have been fundamental in establishing the role of major ions (especially Ca 2+ , H + , K + , and anions) in apical growth.…”