The Ppz protein phosphatases are key regulators of K+ and pH homeostasis: implications for salt tolerance, cell wall integrity and cell cycle progression

Abstract

The yeast Ppz protein phosphatases and the Hal3p inhibitory subunit are important determinants of salt tolerance, cell wall integrity and cell cycle progression. We present several lines of evidence showing that these disparate phenotypes are connected by the fact that Ppz regulates K + transport. First, salt tolerance, cell wall integrity and cell cycle phenotypes of Ppz mutants are dependent on the Trk K + transporters. Secondly, Ppz mutants exhibit altered activity of the Trk system, as measured by rubidium uptake. Thirdly, Ppz mutants exhibit altered intracellular K + and pH, as expected from H + ef¯ux providing electrical balance during K + uptake. Our unifying picture of Ppz phenotypes contends that activation of Trk by decreased Ppz activity results in plasma membrane depolarization (reducing uptake of toxic cations), increased intracellular K + and turgor (compromising cell integrity), and increased intracellular pH (augmenting the expression of pH-regulated genes and facilitating a-factor recovery). In addition to providing a coherent explanation for all Ppz-dependent phenotypes, our results provide evidence for a causal relationship between intracellular cation homeostasis and a potential cell cycle checkpoint.

Protein phosphatase CaPpz1 is involved in cation homeostasis, cell wall integrity and virulence of Candida albicans

“…Furthermore, the C. albicans mutant was tolerant to toxic cations (spermine and hygromycin B), indicating that the absence of CaPpz1 resulted in a depolarization of cell membrane potential that decreased uptake of the toxic agents, as previously found for budding yeast ppz mutants (Yenush et al, 2002). These experiments underline again the similarity between the C. albicans and S. cerevisiae PPZ phosphatases.…”

“…We found that the null mutant was tolerant to LiCl, and was sensitive to KCl. According to these properties it behaves like the S. cerevisiae ppz1 mutant (Posas et al, 1995;Ruiz et al, 2003;Yenush et al, 2002). However, there was a clear-cut difference between the two mutants when sensitivity to NaCl was tested.…”

“…Deletion of ScPPZ2 does not result in a detectable phenotype. However, strains lacking ScPpz1 exhibit increased tolerance to NaCl and LiCl (Posas et al, 1995), altered K + influx, and hypersensitivity to caffeine (Posas et al, 1993;Yenush et al, 2002). On the other hand, overexpression of ScPPZ1 results in slow growth and cell cycle blockage at the G1-S transition (Clotet et al, 1999).…”

“…On the other hand, overexpression of ScPPZ1 results in slow growth and cell cycle blockage at the G1-S transition (Clotet et al, 1999). The effect of the Scppz1 mutation on cation homeostasis is due to the elevated expression of the Na + -ATPase gene ENA1 (Posas et al, 1995;Ruiz et al, 2003) and to the increased influx of potassium ions mediated by the high-affinity K + -transporter Trk1 (Yenush et al, 2002). ScPPZ1 exhibits genetic interactions with SLT2, which encodes a mitogen-activated protein (MAP) kinase required for signalling in the cell wall integrity (CWI) pathway (reviewed by Levin, 2005).…”

Comparative genomics of MAP kinase and calcium–calcineurin signalling components in plant and human pathogenic fungi

“…The serine/threonine protein phosphatases Ppz1 and Ppz2 are key regulators of K + and pH homeostasis, thus determining salt tolerance, cell wall integrity and cell cycle progression (Yenush et al, 2002). In contrast to S. cerevisiae, all fungal species studied with the exception of R. oryzae contain only a single Ppz1 and 2 orthologue.…”