title: The yeast lipin Smp2 couples phospholipid biosynthesis to nuclear membrane growth.
abstract: Remodelling of the nuclear membrane is essential for the dynamic changes of nuclear architecture at different stages of the cell cycle and during cell differentiation. The molecular mechanism underlying the regulation of nuclear membrane biogenesis is not known. Here we show that Smp2, the yeast homologue of mammalian lipin, is a key regulator of nuclear membrane growth during the cell cycle. Smp2 is phosphorylated by Cdc28/Cdk1 and dephosphorylated by a nuclear/endoplasmic reticulum (ER) membrane-localized CPD phosphatase complex consisting of Nem1 and Spo7. Loss of either SMP2 or its dephosphorylated form causes transcriptional upregulation of key enzymes involved in lipid biosynthesis concurrent with a massive expansion of the nucleus. Conversely, constitutive dephosphorylation of Smp2 inhibits cell division. We show that Smp2 associates with the promoters of phospholipid biosynthetic enzymes in a Nem1-Spo7-dependent manner. Our data suggest that Smp2 is a critical factor in coordinating phospholipid biosynthesis at the nuclear/ER membrane with nuclear growth during the cell cycle.
authors.affiliation: WellcomeTrust/Cancer Research UK Gurdon Institute, Cambridge, UK.
authors.forename: Helena
authors.initials: H
authors.lastname: Santos-Rosa
authors.forename: Joanne
authors.initials: J
authors.lastname: Leung
authors.forename: Neil
authors.initials: N
authors.lastname: Grimsey
authors.forename: Sew
authors.initials: S
authors.lastname: Peak-Chew
authors.forename: Symeon
authors.initials: S
authors.lastname: Siniossoglou
mesh_terms: D017489:CDC28 Protein Kinase, S cerevisiae / Q000378:metabolism; D002453:Cell Cycle; D004721:Endoplasmic Reticulum / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D008055:Lipids / Q000096:biosynthesis; D008563:Membrane Lipids / Q000096:biosynthesis*; D008565:Membrane Proteins / Q000378:metabolism; D008938:Mitosis; D009097:Multienzyme Complexes; D009685:Nuclear Envelope / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D010711:Phosphatidate Phosphatase; D010743:Phospholipids / Q000096:biosynthesis*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000235:genetics; D011499:Protein Processing, Post-Translational; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism / Q000502:physiology*
chemical_list: D008055:Lipids; D008563:Membrane Lipids; D008565:Membrane Proteins; D009097:Multienzyme Complexes; C502372:Nem1 protein, S cerevisiae; D009687:Nuclear Proteins; D010743:Phospholipids; D011993:Recombinant Fusion Proteins; C116365:SPO7 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D017489:CDC28 Protein Kinase, S cerevisiae; C079831:PAH1 protein, S cerevisiae; D010711:Phosphatidate Phosphatase