The yeast model for batten disease: mutations in BTN1, BTN2, and HSP30 alter pH homeostasis

J Bacteriol. 2000 Nov;182(22):6418-23. doi: 10.1128/JB.182.22.6418-6423.2000.

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-Delta 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-Delta strains compensate for the altered plasma membrane H(+)-ATPase activity and vacuolar pH by elevating the expression of the two genes HSP30 and BTN2. We now show that deletion of either HSP30 or BTN2 in either BTN1(+) or btn1-Delta 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 of HSP30 and BTN2 in btn1-Delta strains and diminished growth of btn1-Delta, hsp30-Delta, and btn2-Delta strains at low pH reinforce our view that altered pH homeostasis is the underlying cause of Batten disease.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Culture Media
  • Cyclins*
  • Cytosol / metabolism
  • Fungal Proteins / analysis
  • Fungal Proteins / genetics*
  • HSP30 Heat-Shock Proteins
  • Heat-Shock Proteins / genetics*
  • Homeostasis
  • Humans
  • Hydrogen-Ion Concentration
  • Membrane Glycoproteins*
  • Membrane Proteins / genetics*
  • Molecular Chaperones*
  • Mutation
  • Neuronal Ceroid-Lipofuscinoses / microbiology*
  • Proton-Translocating ATPases / metabolism
  • Saccharomyces cerevisiae Proteins*
  • Sorbic Acid
  • Vacuoles / metabolism
  • Yeasts / genetics*
  • Yeasts / growth & development

Substances

  • CLN3 protein, human
  • Culture Media
  • Cyclins
  • Fungal Proteins
  • HSP30 Heat-Shock Proteins
  • Heat-Shock Proteins
  • Membrane Glycoproteins
  • Membrane Proteins
  • Molecular Chaperones
  • Saccharomyces cerevisiae Proteins
  • YHC3 protein, S cerevisiae
  • Proton-Translocating ATPases
  • Sorbic Acid