Cdc1p is an ER-localized Putative Lipid Phosphatase that Affects Golgi Inheritance and Actin Polarization by Activating Ca²⁺ Signaling

Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL 60637, USA

^* To whom correspondence should be addressed. Email: bsglick{at}uchicago.edu.

	Abstract

In the budding yeast Saccharomyces cerevisiae, mutations in the essential gene CDC1 cause defects in Golgi inheritance and actin polarization. However, the biochemical function of Cdc1p is unknown. Previous work showed that cdc1 mutants accumulate intracellular Ca²⁺ and display enhanced sensitivity to the extracellular Mn²⁺ concentration, suggesting that Cdc1p might regulate divalent cation homeostasis. By contrast, our data indicate that Cdc1p is a Mn²⁺-dependent protein that can affect Ca²⁺ levels. We identified a cdc1 allele that activates Ca²⁺ signaling but does not show enhanced sensitivity to the Mn²⁺ concentration. Furthermore, our studies show that Cdc1p is an ER-localized transmembrane protein with a putative phosphoesterase domain facing the lumen. cdc1 mutant cells accumulate an unidentified phospholipid, suggesting that Cdc1p may be a lipid phosphatase. Previous work showed that deletion of the plasma membrane Ca²⁺ channel Cch1p partially suppressed the cdc1 growth phenotype, and we find that deletion of Cch1p also suppresses the Golgi inheritance and actin polarization phenotypes. The combined data fit a model in which the cdc1 mutant phenotypes result from accumulation of a phosphorylated lipid that activates Ca²⁺ signaling.