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

Takahashi, Osamu; Hirata, Dai; Usui, Hirofumi; Nishito, Yasumasa; Miyakawa, Tokichi; Igarashi, Kazuhiko; Takeda, Masao

doi:10.1046/j.1365-2443.2001.00429.x

Cited by 18 publications

(24 citation statements)

References 50 publications

(106 reference statements)

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“…At the same time, S. pombe pab1-4 cells lose growth polarity and manifest disorganized microtubule arrays and delocalized cortical actin patches ( Figure 6A), a phenotype in agreement with previous studies of the pab1 null allele, which established a positive role for PP2A-Pab1 in morphogenesis (Kinoshita et al 1996;Jiang and Hallberg 2000;Tanabe et al 2001). Thus, PP2A-Pab1 seems to play a dual function: negative regulation of cell division with a positive role in morphogenesis.…”

Section: Resultssupporting

confidence: 90%

“…In S. pombe, there are two genes encoding the B9-regulatory subunits, par1 and par2. The double null mutant is viable, but is sensitive to temperature (high and low) and stress and shows defects in septation and cleavage ( Jiang and Hallberg 2000;Tanabe et al 2001). Curiously, a mutation in the regulatory subunit B9 Par1 is able to suppress the septation defects of cdc11-136, cdc7-24, spg1-B8 (Le Goff et al 2001), and sid2-250 mutants ( Jin et al 2006).…”

Section: Resultsmentioning

confidence: 99%

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Antagonistic Roles of PP2A-Pab1 and Etd1 in the Control of Cytokinesis in Fission Yeast

et al. 2010

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In Schizosaccharomyces pombe, Etd1 is a positive regulator of the septation initiation network (SIN), a conserved GTPase-regulated kinase cascade that triggers cytokinesis. Here we show that a mutation in the pab1 gene, which encodes the B-regulatory subunit of the protein phosphatase 2A (PP2A), suppresses mutations in the etd1 gene. Etd1 is required for the function of the GTPase Spg1, a key regulator of SIN signaling. Interestingly, the loss of Pab1 function restored the activity of Spg1 in Etd1-deficient cells. This result suggests that PP2A-Pab1-mediated dephosphorylation inhibits Spg1, thus antagonizing Etd1 function. The loss of pab1 function also rescues the lethality of mutants of other genes in the SIN cascade such as mob1, sid1, and cdc11. Two-hybrid assays indicate that Pab1 physically interacts with Mob1, Sid1, Sid2, and Cdc11, suggesting that the phosphatase 2A B-subunit is a component of the SIN complex. Together, our results indicate that PP2A-Pab1 plays a novel role in cytokinesis, regulating SIN activity at different levels. Pab1 is also required to activate polarized cell growth. Thus, PP2A-Pab1 may be involved in coordinating polar growth and cytokinesis.

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Section: Resultssupporting

confidence: 90%

Section: Resultsmentioning

confidence: 99%

Antagonistic Roles of PP2A-Pab1 and Etd1 in the Control of Cytokinesis in Fission Yeast

et al. 2010

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“…The phenotype of the pab1-D mutant suggests that this form of PP2A is important for cell morphogenesis (Kinoshita et al 1996;Tanabe et al 2001;Lahoz et al 2010). The similarity of this to the ppa2-6 and ypa2-D indicates that PP2A plays an important role in cell morphogenesis and also implicates Ypa2p in this process.…”

Section: S Pombe Ptpa Genesmentioning

confidence: 84%

“…The par1 and par2 genes encode the two B9-family subunits. Par1p is the major form (Jiang and Hallberg 2000;Le Goff et al 2001;Tanabe et al 2001); deletion of par1 affects septum positioning and also renders cells cold sensitive and hypersensitive to loss of PP2B/calcineurin (Jiang and Hallberg 2000;Le Goff et al 2001;Tanabe et al 2001); in contrast, deletion of par2 has little effect on the cell per se (Jiang and Hallberg 2000;Tanabe et al 2001).…”

Section: Pp2a In S Pombementioning

confidence: 99%

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

Goyal

2012

Genetics

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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-D ypa2-D null 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-D 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 NetworkThe 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 Garcia-Cortes and McCollu...

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“…Protein phosphatases Par1p and Par2p all act negatively on septation as deletion of par1 and par2 genes leads to a phenotype with multiple septa formed between daughter cells ( Jiang and Hallberg 2000;Tanabe et al 2001). The par1 gene also was isolated as an extragenic suppressor of loss-of-function mutation in the spg1 gene (Le Goff et al 2001).…”

Section: Discussionmentioning

confidence: 99%

Isolation of Mutations That Bypass the Requirement of the Septation Initiation Network for Septum Formation and Conidiation inAspergillus nidulans

et al. 2006

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The kinase cascade of the septation initiation network (SIN), first revealed in fission yeast, activates the contraction of the actomyosin ring, and plays an essential role in fungal septation. Mob1p, an evolutionarily conserved SIN protein, is associated with the most downstream kinase of this cascade in fission yeast. In this study, the mobA gene encoding a homologous protein was isolated from the filamentous fungus Aspergillus nidulans, whose mycelium is made of multinucleate cells. The MOBA protein was required for septation and conidiation, but was not essential for hyphal extension and colony formation. To identify genes that act antagonistically against the SIN, UV mutagenesis was carried out to isolate suppressor (smo) mutations that restored conidiation when MOBA was not expressed. Microscopic examination indicated that the restored conidiation was concomitant with restored septation in the absence of the MOBA protein. Eight recessive smo mutations in five complementation groups also bypassed the requirement of the SIN kinases SEPH and SIDB for septum formation and conidiation. However, none of these smo mutations affected the localization of MOBA. Among smo mutations, smoA and smoB mutations caused reduced hyphal growth and colony formation. They also rendered hypersensitivity to low doses of the microtubule-depolymerizing agent benomyl for conidiation. Therefore, in A. nidulans, proteins encoded by the smo genes likely have an antagonistic interaction against the SIN pathway to regulate septation and conidiation.

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

Cited by 18 publications

References 50 publications

Antagonistic Roles of PP2A-Pab1 and Etd1 in the Control of Cytokinesis in Fission Yeast

Antagonistic Roles of PP2A-Pab1 and Etd1 in the Control of Cytokinesis in Fission Yeast

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

Isolation of Mutations That Bypass the Requirement of the Septation Initiation Network for Septum Formation and Conidiation inAspergillus nidulans

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