VPH6 MUTANTS OF SACCHAROMYCES-CEREVISIAE REQUIRE CALCINEURIN FOR GROWTH AND ARE DEFECTIVE IN VACUOLAR H-ATPASE ASSEMBLY()

Citation
Cs. Hemenway et al., VPH6 MUTANTS OF SACCHAROMYCES-CEREVISIAE REQUIRE CALCINEURIN FOR GROWTH AND ARE DEFECTIVE IN VACUOLAR H-ATPASE ASSEMBLY(), Genetics, 141(3), 1995, pp. 833-844
Citations number
75
Categorie Soggetti
Genetics & Heredity
Journal title
ISSN journal
00166731
Volume
141
Issue
3
Year of publication
1995
Pages
833 - 844
Database
ISI
SICI code
0016-6731(1995)141:3<833:VMOSRC>2.0.ZU;2-9
Abstract
We have characterized a Saccharomyces cerevisiae mutant strain that is hypersensitive to cyclosporin A (CsA) and FK506, immunosuppressants t hat inhibit calcineurin, a serine-threonine-specific phosphatase (PP2B ). A single nuclear mutation, designated cev1 for calcineurin essentia l for viability, is responsible for the CsA-FK506-sensitive phenotype. The peptidyl-prolyl cis-trans isomerases cyclophilin A and FKBP12, re spectively, mediate CsA and FK506 toxicity in the cev1 mutant strain. We demonstrate that cev1 is an allele of the VPH6 gene and that vph6 m utant strains fail to assemble the vacuolar H+-ATPase (V-ATPase). The VPH6 gene was mapped on chromosome VIII and is predicted to encode a 1 81-amino acid (21 kD) protein with no identity to other known proteins . Sire find that calcineurin is essential for viability in many mutant strains with defects in V-ATPase function or vacuolar acidification. In addition, we find that calcineurin modulates extracellular acidific ation in response to glucose, which we propose occurs via calcineurin regulation of the plasma membrane H+-ATPase PMA1. Taken together, our findings suggest calcineurin plays a general role in the regulation of cation transport and homeostasis.