Regulation of Vacuolar H + ATPase Subunit Expression in the Mouse Brain by Developmental Stage and pH Changes.

The vacuolar-type H ATPase (V-ATPase) is a ubiquitously expressed proton pump, essential for multiple cellular processes such as acidification of intracellular organelles. The V-ATPase consists of a transmembrane domain (V0) responsible for proton translocation and a cytosolic domain (V1) which catalyzes ATP hydrolysis. The functional domains contain different subunits with tissue-specific expression patterns. In some organs, such as the kidney and salivary glands, V-ATPase is located in the plasma membrane and previous studies have shown that its subunits are regulated by acid-base disturbances. It has also been proposed that V-ATPase subunits may be regulated by growth factors. In the present study, QRT-PCR was used to examine the expression of different V-ATPase subunits in the mouse brain and kidney in different developmental stages. Additionally, we have examined the impact of Transforming Growth Factor β2 (TGF-β2) on different subunit expression, as well as their regulation in mouse cortical astrocytes following extracellular acidosis. The results show that the subunits ATP6V1A1, ATP6V1C1 and ATP6V1B2 are more abundant in the mouse brain, compared to kidney. In contrast, expression of subunits ATP6V1C2 and ATP6V1G3 is higher in the kidney, compared to brain. Our data also reveal developmental changes of subunit transcriptional levels in the mouse brain. Subunit ATP6V1G1 expression is decreasing during brain development, while the expression of ATP6V1C1 is developmentally increasing in the mouse brain. Moreover, our data indicate differential regulation of distinct V-ATPase subunits in mouse embryonic brain and kidney by TGF-β2. Extracellular acidosis has no effect on ATP6V1A1, ATP6V1C1 and ATP6V1E1 transcript levels in cortical astrocytes. Our data provide first evidence on developmental regulation of V-ATPase subunits in the brain.