ABSTRACT
The BTN1 gene product of the yeast Saccharomyces cerevisiae is 39% identical and 59% similar to human CLN3, which is associated with the neurodegenerative disorder Batten disease. Furthermore, btn1-Δ strains have an elevated activity of the plasma membrane H+-ATPase due to an abnormally high vacuolar acidity during the early phase of growth. Previously, DNA microarray analysis revealed that btn1-Δ strains compensate for the altered plasma membrane H+-ATPase activity and vacuolar pH by elevating the expression of the two genesHSP30 and BTN2. We now show that deletion of either HSP30 or BTN2 in eitherBTN1
+ or btn1-Δ strains does not alter vacuolar pH but does lead to an increased activity of the vacuolar H+-ATPase. Deletion of BTN1,BTN2, or HSP30 does not alter cytosolic pH but diminishes pH buffering capacity and causes poor growth at low pH in a medium containing sorbic acid, a condition known to result in disturbed intracellular pH homeostasis. Btn2p was localized to the cytosol, suggesting a role in mediating pH homeostasis between the vacuole and plasma membrane H+-ATPase. Increased expression ofHSP30 and BTN2 in btn1-Δ strains and diminished growth of btn1-Δ, hsp30-Δ, and btn2-Δ strains at low pH reinforce our view that altered pH homeostasis is the underlying cause of Batten disease.
An integrative view on vacuolar pH‐homeostasis in
Arabidopsis thaliana
: Combining mathematical modeling and experimentation