Fission yeast homologues of the B′ subunit of protein phosphatase 2A: multiple roles in mitotic cell division and functional interaction with calcineurin

Background Protein phosphatase 2A (PP2A) is a serine/threonine phosphatase distributed in eukaryotes from yeast to human, and plays pivotal roles in diverse cellular functions such as metabolism, cell cycle progression, gene expression and development. PP2A holoenzyme is a heterodimer of a catalytic subunit C and a regulatory subunit A, or a heterotrimer of C, A and a variable regulatory subunit consisting of three families; B, B′, and PR72. Specific functions for each variable subunit are not well understood. Results Summary figure Two fission yeast genes pbp1+ and pbp2+ homologous to the regulatory subunit B′ were isolated. Physical in vivo interaction of the gene products with the catalytic subunit was demonstrated. A double disruption haploid mutant (Δpbp1Δpbp2) showed growth defect, cell shape and size abnormality, multiseptation and anucleated cell formation due to abnormality in septum positioning. These phenotypes were suppressed by human B′ cDNA, indicating the striking conservation of the B′ function from yeast to human. Over-expression of fission yeast B′ led to growth defects, a loss of cell shape polarity, septal abnormality and anucleated cell formation. Δpbp1Δpbp2 and pbp1 null haploids were hypersensitive to calcineurin inhibitors, cyclosporin A and FK506, with which the mutants underwent arrest at post-anaphase and cell lysis. Double disruption of calcineurin and pbp1+, but not pbp2+, genes led to synthetic lethality. Figure Summary figure . Roles of B′ and its functional interaction with calcineurin in fission yeast. This hypothetical summary scheme is depicted based on the observations in this study and others (Jiang & Hallberg 2000; Sugiura et al. 1998; Yoshida et al. 1994). CAB′ is the trimeric holoenzyme of PP2A containing B′ as a variable regulatory subunit. Download figure to PowerPoint Conclusion The fission yeast B′ subunit of PP2A plays critical roles in cell shape control and septum formation, and shares essential functions with calcineurin for viability, possibly through their roles in cytokinesis and cell wall integrity.