Metabolism of inositol 1,4,5-trisphosphate in Candida albicans: Significance as a precursor of inositol polyphosphates and in signal transduction during the dimorphic transition from yeast cells to germ tubes

The metabolism of inositol 1,4,5-trisphosphate [lns(1,4,5)P-3] was examined in yeast cells and germ tubes of Candida albicans. Methods have been developed for analysis of the two key metabolic enzymes, lns(1,4,5)P-3 kinase and phosphatase. ATP-dependent lns(1,4,5)P-3 kinase activity was detected predominantly in the soluble fraction of cell extracts and exhibited a K-m of approximately 9 mu M. The apparent K-m of lns(1,4,5)P-3 phosphatase for lns(1,4,5)P, was approximately 480 mu M. The slow rate of dephosphorylation of lns(1,4,5)P, to inositol bisphosphate suggests a lower importance of the phosphatase within cells compared to the kinase. Since both yeast cells and germ tubes of C. albicans rapidly phosphorylated lns(1,4,5)P-3 to inositol tetrakisphosphate and inositol penta/hexakisphosphate, it is suggested that lns(1,4,5)P-3 has an important role as a precursor for production of these compounds. A sustained increase in cellular lns(1,4,5)P-3 levels was observed during germ tube formation and, prior to the onset of germination between 1 and 2 h incubation, the lns(1,4,5)P-3 content increased up to eightfold. Transient increases in the level of lns(1,4,5)P, were also observed during yeast-like growth of C. albicans. The possible role and relative importance of lns(1,4,5)P-3 as a precursor for inositol polyphosphates and in signal transduction involving Ca2+ release from internal stores is discussed.