Journal of Bacteriology, November 2000, p. 6418-6423, Vol. 182, No. 22
0021-9193/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Center for Aging and Developmental Biology1 and the Department of Biochemistry and Biophysics,2 University of Rochester Medical School, Rochester, New York 14642
Received 29 March 2000/Accepted 22 August 2000
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-
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-
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-
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-
strains and diminished growth of btn1-
, hsp30-
,
and btn2-
strains at low pH reinforce our view that
altered pH homeostasis is the underlying cause of Batten disease.
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