Lipid signaling via Pkh1/2 regulates fungal CO2 sensing through the kinase Sch9

Adaptation to alternating CO2 concentrations is crucial for all organisms. Carbonic anhydrases – metalloenzymes that have been found in all domains of life - enable fixation of scarce CO2 by accelerating its conversion to bicarbonate and ensure maintenance of cellular metabolism. In fungi and other eukaryotes, the carbonic anhydrase Nce103 has been shown to be essential for growth in air (~0.04% CO2). Expression of NCE103 is regulated in response to CO2-availability. In Saccharomyces cerevisiae, NCE103 is activated by the transcription factor ScCst6, in Candida albicans and Candida glabrata by its homologue Ca/CgRca1. To identify the kinase controlling Cst6/Rca1, we screened a S. cerevisiae kinase/phosphatase mutant library for the ability to regulate NCE103 in a CO2-dependent manner. We identified ScSch9 as potential ScCst6-specific kinase, as the sch9∆ mutant strain showed deregulated NCE103 expression on RNA and protein level. Immunoprecipitation revealed binding capability of both proteins and detection of ScCst6 phosphorylation by ScSch9 in vitro confirmed Sch9 as the Cst6 kinase. We could show that CO2-dependent activation of Sch9, which is part of a kinase cascade, is mediated by lipid / Pkh1/2 signaling but not TORC1. Finally, we tested conservation of the identified regulatory cascade in the pathogenic yeast species C. albicans and C. glabrata. Deletion of SCH9 homologues of both species impaired CO2-dependent regulation of NCE103 expression, which indicates a conservation of CO2 adaptation mechanism among yeasts. Thus, Sch9 is a Cst6/Rca1 kinase that links CO2 adaptation to lipid signaling via Pkh1/2 in fungi.

Publication year:2017

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BOF-publication weight:6

CSS-citation score:1

Authors:International

Authors from:Higher Education

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