FXYD8, a Novel Regulator of Renal Na+/K+-ATPase in the Euryhaline Teleost, Tetraodon nigroviridis.

Pei-Jen Wang,Wen-Kai Yang,Hau-Hsuan Hwang,Tsung-Han Lee,Chia-Hao Lin

doi:10.3389/fphys.2017.00576

Abstract

FXYD proteins are important regulators of Na+/K+-ATPase (NKA) activity in mammals. As an inhabitant of estuaries, the pufferfish (Tetraodon nigroviridis) responds to ambient salinity changes with efficient osmoregulation, including alterations in branchial, and renal NKA activities. Previous studies on teleostean FXYDs have mainly focused on the expression and potential functions of FXYD proteins in gills. The goal of the present study was to elucidate the potential role of FXYD8, a member of the fish FXYD protein family, in the modulation of NKA activity in the kidneys of this euryhaline pufferfish by using molecular, biochemical, and physiological approaches. The results demonstrate that T. nigroviridis FXYD8 (TnFXYD8) interacts with NKA in renal tubules. Meanwhile, the protein expression of renal TnFXYD8 was found to be significantly upregulated in hyperosmotic seawater-acclimated pufferfish. Moreover, overexpression of TnFXYD8 in Xenopus oocytes decreased NKA activity. Our results suggest the FXYD8 is able to modulate NKA activity through inhibitory effects upon salinity challenge. The present study further extends our understanding of the functions of FXYD proteins, the regulators of NKA, in vertebrates.

Highlights

Na+/K+-ATPase (NKA) is a ubiquitous membrane-bound protein complex that actively maintains the Na+ and K+ gradient between the intra- and extracellular milieu of animal cells, and plays a crucial role in osmoregulation and ion exchange (Scheiner-Bobis, 2002; Marshall and Grosell, 2006; Hwang and Lee, 2007)
To elucidate the regulatory mechanisms of renal NKA activity in pufferfish with efficient responses to ambient salinity challenge, we aimed to investigate patterns of T. nigroviridis FXYD8 (TnFXYD8) mRNA/protein expression
FXYD8 is a novel member of the FXYD protein family in euryhaline teleosts, and this study investigated the localization and interaction between TnFXYD8 and NKA in the kidneys of pufferfish acclimated to FW and SW

Summary

Introduction

Na+/K+-ATPase (NKA) is a ubiquitous membrane-bound protein complex that actively maintains the Na+ and K+ gradient between the intra- and extracellular milieu of animal cells, and plays a crucial role in osmoregulation and ion exchange (Scheiner-Bobis, 2002; Marshall and Grosell, 2006; Hwang and Lee, 2007). It is a P-type ATPase consisting of an (αβ) protein complex (ScheinerBobis, 2002; Toyoshima et al, 2011). Several mechanisms have been reported to be involved in the regulation of NKA activity, including the FXYD proteins (Scheiner-Bobis, 2002; Crambert and Geering, 2003; Geering, 2008)

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