Academic journal article Genetics

Characterization of Ypa1 and Ypa2, the Schizosaccharomyces Pombe Orthologs of the Peptidyl Proyl Isomerases That Activate PP2A, Reveals a Role for Ypa2p in the Regulation of Cytokinesis

Academic journal article Genetics

Characterization of Ypa1 and Ypa2, the Schizosaccharomyces Pombe Orthologs of the Peptidyl Proyl Isomerases That Activate PP2A, Reveals a Role for Ypa2p in the Regulation of Cytokinesis

Article excerpt

ABSTRACT The Schizosaccharomyces pombe septation initiation network (SIN) regulates cytokinesis. Cdc7p is the first kinase in the core SIN; we have screened genetically for SIN regulators by isolating cold-sensitive suppressors of cdc7-24. Our screen yielded a mutant in SPAC1782.05, one of the two fission yeast orthologs of mammalian phosphotyrosyl phosphatase activator. We have characterized this gene and its ortholog SPAC4F10.04, which we have named ypa2 and ypa1, respectively. We find that Ypa2p is the major form of protein phosphatase type 2A activator in S. pombe. A double ypa1-Δ ypa2-DΔnull mutant is inviable, indicating that the two gene products have at least one essential overlapping function. Individually, the ypa1 and ypa2 genes are essential for survival only at low temperatures. The ypa2-Δ mutant divides at a reduced cell size and displays aberrant cell morphology and cytokinesis. Genetic analysis implicates Ypa2p as an inhibitor of the septation initiation network. We also isolated a cold-sensitive allele of ppa2, the major protein phosphatase type 2A catalytic subunit, implicating this enzyme as a regulator of the septation initiation network.

SCHIZOSACCHAROMYCES pombe cells take the form of a cylinder capped by hemispherical ends. During interphase, cells grow mainly at their tips. Cell elongation ceases after mitotic commitment, and the cytoskeleton is reorganized in preparation for nuclear and cell division (reviewed by McCully and Robinow 1971; Mitchison and Nurse 1985; Marks et al. 1986; Hagan and Hyams 1988; Hagan 1998). The cell divides by fission after forming a septum in the middle of the cell. The site of division is defined at the onset of mitosis (Daga and Chang 2005), by the formation of an actomyosin contractile ring (CAR), whose assembly continues throughout mitosis (Wu et al. 2003; Pollard 2008; Pollard and Wu 2010). At the end of anaphase, the CAR is thought to guide synthesis of the multilayered division septum (reviewed by (Ishiguro 1998; Sipiczki 2007).

Septation Initiation Network

The S. pombe septation initiation network (SIN) is a network of protein kinases that is essential for cytokinesis in the mitotic cycle; reviewed by (Gould and Simanis 1997; Simanis 2003; Wolfe and Gould 2005; Goyal et al. 2011). It is tightly regulated through the mitotic cell cycle to assure proper coordination of mitosis and cytokinesis, and during meiosis, where it is essential for spore formation (Krapp et al. 2006). Signaling requires the activity of three protein kinases, each of which has a regulatory subunit (kinase regulator); Cdc7p-Spg1p (Fankhauser and Simanis 1994; Schmidt et al. 1997; Mehta and Gould 2006), Sid1p-Cdc14p (Fankhauser and Simanis 1993; Guertin et al. 2000; Guertin and McCollum 2001), and Sid2p-Mob1p (Sparks et al. 1999; Hou et al. 2000; Salimova et al. 2000). SIN signaling is modulated by the nucleotide status of the GTPase Spg1p (Schmidt et al. 1997; Sohrmann et al. 1998), which is determined by the balance of spontaneous nucleotide exchange, a putative GEF, Etd1p (Daga et al. 2005; Garcia-Cortes and McCollum 2009), and a GAP, Cdc16p (Minet et al. 1979; Fankhauser et al. 1993), with which Spg1p interacts through a scaffold, Byr4p (Song et al. 1996; Furge et al. 1998; Furge et al. 1999). The SIN is also activated by the mitotic regulator Plo1p (Tanaka et al. 2001). Loss of SIN signaling produces multinucleated cells, while constitutive activation of the SIN results in multiseptated cells (Minet et al. 1979; Fankhauser et al. 1993; Song et al. 1996). Ectopic activation of the SIN promotes CAR and septum formation from any stage of the cell cycle (Fankhauser and Simanis 1994; Ohkura et al. 1995; Schmidt et al. 1997; Guertin et al. 2002). Analysis of the localization of SIN proteins and their activity in mutant backgrounds has led to the proposition that the order of action of the SIN proteins in the mitotic cell cycle is Cdc7p-Spg1p, then Sid1p- Cdc14p, and finally Sid2p-Mob1p (Sparks et al. …

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