Its8, a fission yeast homolog of Mcd4 and Pig-n, is involved in GPI anchorsynthesis and shares an essential function with calcineurin in cytokinesis

In fission yeast, calcineurin is required for cytokinesis and ion homeostas is; however, most of its physiological roles remain obscure. To identify ge nes that share an essential function with calcineurin, we screened for muta tions that confer sensitivity to the calcineurin inhibitor FK506 and high t emperature and isolated the mutant its8-1. its8(+) encodes a homolog of the budding yeast MCD4 and human Pig-n that are involved in glycosylphosphatid ylinositol (GPI) anchor synthesis. Consistently, reduced inositol labeling of proteins suggested impaired GPI anchor synthesis in its8-1 mutants. The temperature upshift induced a further decrease in inositol labeling and cau sed dramatic increases in the frequency of septation in its8-1 mutants. BE4 9385A, an inhibitor of MCD4 and Pig-n, also increased the septation index o f the wild-type cell. Osmotic stabilization suppressed these morphological defects, indicating that cell wall weakness caused by impaired GPI anchor s ynthesis resulted in abnormal cytokinesis. Furthermore, calcineurin-deleted cells exhibited hypersensitivity to BE49385A, and FK506 exacerbated the cy tokinesis defects of the its8-1 mutant, Thus, calcineurin and Its8 may shar e an essential function in cytokinesis and cell viability through the regul ation of cell wall integrity.