Extra-renal locations of the a4 subunit of H(+)ATPase.

Zoe J Golder,Fiona E Karet Frankl

doi:10.1186/s12860-016-0106-8

Abstract

BackgroundVacuolar-type proton pumps help maintain acid–base homeostasis either within intracellular compartments or at specialised plasma membranes. In mammals they are made up of 13 subunits, which form two functional domains. A number of the subunits have variants that display tissue restricted expression patterns such that in specialised cell types they replace the generic subunits at some sub-cellular locations. The tissue restricted a4 subunit has previously been reported at the plasma membrane in the kidney, inner ear, olfactory epithelium and male reproductive tract.ResultsIn this study novel locations of the a4 subunit were investigated using an Atp6v0a4 knockout mouse line in which a LacZ reporter cassette replaced part of the gene. The presence of a4 in the olfactory epithelium was further investigated and the additional presence of C2 and d2 subunits identified. The a4 subunit was found in the uterus of pregnant animals and a4 was identified along with d2 and C2 in the embryonic visceral yolk sac. In the male reproductive tract a4 was seen in the novel locations of the prostatic alveoli and the ampullary glands as well as the previously reported epididymis and vas deferens.ConclusionsThe identification of novel locations for the a4 subunit and other tissue-restricted subunits increases the range of unique subunit combinations making up the proton pump. These studies suggest additional roles of the proton pump, indicating a further range of homologue-specific functions for tissue-restricted subunits.Electronic supplementary materialThe online version of this article (doi:10.1186/s12860-016-0106-8) contains supplementary material, which is available to authorized users.

Highlights

Vacuolar-type proton pumps help maintain acid–base homeostasis either within intracellular compartments or at specialised plasma membranes
Olfactory system β-galactosidase (β-gal) staining and immunostaining in embryonic Atp6v0a4+/− olfactory epithelium Previous work examining whole-mount cleared embryos revealed that β-gal activity, which is driven by the a4 promoter in this model, was present in the nasal cavity from e12.5 onwards [21]
Moving anterior to posterior along the cavity the staining becomes more specific to cells in the location of the future olfactory epithelium (OE) (Fig. 1a)

Summary

Introduction

Vacuolar-type proton pumps help maintain acid–base homeostasis either within intracellular compartments or at specialised plasma membranes In mammals they are made up of 13 subunits, which form two functional domains. The vacuolar type proton pump, or H+ATPase, is responsible for ATP dependent proton movement across membranes of intracellular organelles such as lysosomes where maintenance of pH is important for organelle function. In higher organisms such pumps are found at the plasma membranes of specialised epithelial cells such as those of the kidney, inner ear, and male reproductive tract [1,2,3]. The different combinations of subunits found in specialised locations are hypothesised to allow regulation of trafficking and activity [6]

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Conclusion