Cooperation of calcineurin and vacuolar H(+)-ATPase in intracellular Ca2+ homeostasis of yeast cells.

The Journal of Biological Chemistry
I TanidaY Anraku

Abstract

Saccharomyces cerevisiae VMA genes, encoding essential components for the expression of vacuolar membrane H(+)-ATPase activity, are involved in intracellular ionic homeostasis and vacuolar biogenesis. We report here that the immunosuppressants FK506 and cyclosporin A cause general growth inhibition of the vma3 mutant. Upon addition of the drugs, the mutant grew neither in the presence of more than 5 mM Ca2+ nor above pH 6.0. The action of the immunosuppressants is dependent on their binding proteins and ascribable to inhibition of calcineurin activity; a mutation of a calcineurin subunit (cnb1) shows synthetic lethal interaction with the vma mutation. The addition of FK506 decreases the cytosolic free concentration of Ca2+ in the vma3 mutant cells. Consequently, FK506 induces an 8.9-fold elevation of a nonexchangeable Ca2+ pool. These results suggest that calcineurin controls calcium homeostasis by repression of Ca2+ flux into a cellular compartment(s) and that the vacuolar H(+)-ATPase is essential for cell growth cooperating with calcineurin to regulate the cytosolic free concentration of Ca2+.

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Citations

Aug 13, 2009·Journal of Mathematical Biology·Fusheng Tang, Weijiu Liu
May 13, 2006·Journal of Bioenergetics and Biomembranes·Patricia M Kane
Jun 30, 2011·The Journal of Biological Chemistry·Ryohei TsubakiyamaDai Hirata
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Jul 3, 2016·FEMS Yeast Research·Hiroshi NishikawaHiroshi Mukae
Jun 2, 2017·Molecular Biology of the Cell·Farzan GhanegolmohammadiYoshikazu Ohya
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Jul 26, 2013·The Journal of Biological Chemistry·Cassandra PatenaudeRajini Rao
Jan 26, 2020·IUBMB Life·Sindhuja Gowrisankaran, Ira Milosevic
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