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Mol. Cell. Biol., 05 1996, 2226-2237, Vol 16, No. 5
KW Cunningham and GR Fink
The PMC1 gene in Saccharomyces cerevisiae encodes a vacuolar Ca2+ ATPase
required for growth in high-Ca2+ conditions. Previous work showed that Ca2+
tolerance can be restored to pmc1 mutants by inactivation of calcineurin, a
Ca2+/calmodulin-dependent protein phosphatase sensitive to the
immunosuppressive drug FK506. We now report that calcineurin decreases Ca2+
tolerance of pmc1 mutants by inhibiting the function of VCX1, which encodes
a vacuolar H+/Ca2+ exchanger related to vertebrate Na+/Ca2+ exchangers. The
contribution of VCX1 in Ca2+ tolerance is low in strains with a functional
calcineurin and is high in strains which lack calcineurin activity. In
contrast, the contribution of PMC1 to Ca2+ tolerance is augmented by
calcineurin activation. Consistent with these positive and negative roles
of calcineurin, expression of a vcx1::lacZ reporter was slightly diminished
and a pmc1::lacZ reporter was induced up to 500-fold by processes dependent
on calcineurin, calmodulin, and Ca2+. It is likely that calcineurin
inhibits VCX1 function mainly by posttranslational mechanisms. Activities
of VCX1 and PMC1 help to control cytosolic free Ca2+ concentrations because
their function can decrease pmc1::lacZ induction by calcineurin. Additional
studies with reporter genes and mutants indicate that PMR1 and PMR2A,
encoding P-type ion pumps required for Mn2+ and Na+ tolerance, may also be
induced physiologically in response to high-Mn2+ and -Na+ conditions
through calcineurin-dependent mechanisms. In these situations, inhibition
of VCX1 function may be important for the production of Ca2+ signals. We
propose that elevated cytosolic free Ca2+ concentrations, calmodulin, and
calcineurin regulate at least four ion transporters in S. cerevisiae in
response to several environmental conditions.
Copyright © 1996, American Society for Microbiology
Calcineurin inhibits VCX1-dependent H+/Ca2+ exchange and induces Ca2+ ATPases in Saccharomyces cerevisiae
Department of Biology, Johns Hopkins University, Baltimore, Maryland 21218, USA.
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