title: Mitotic lamin disassembly is triggered by lipid-mediated signaling.
abstract: Disassembly of the nuclear lamina is a key step during open mitosis in higher eukaryotes. The activity of several kinases, including CDK1 (cyclin-dependent kinase 1) and protein kinase C (PKC), has been shown to trigger mitotic lamin disassembly, yet their precise contributions are unclear. In this study, we develop a quantitative imaging assay to study mitotic lamin B1 disassembly in living cells. We find that CDK1 and PKC act in concert to mediate phosphorylation-dependent lamin B1 disassembly during mitosis. Using ribonucleic acid interference (RNAi), we showed that diacylglycerol (DAG)-dependent PKCs triggered rate-limiting steps of lamin disassembly. RNAi-mediated depletion or chemical inhibition of lipins, enzymes that produce DAG, delayed lamin disassembly to a similar extent as does PKC inhibition/depletion. Furthermore, the delay of lamin B1 disassembly after lipin depletion could be rescued by the addition of DAG. These findings suggest that lipins activate a PKC-dependent pathway during mitotic lamin disassembly and provide evidence for a lipid-mediated mitotic signaling event.
authors.affiliation: European Molecular Biology Laboratory, 69117 Heidelberg, Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Mall
authors.forename: Thomas
authors.initials: T
authors.lastname: Walter
authors.forename: Mátyás
authors.initials: M
authors.lastname: Gorjánácz
authors.forename: Iain F
authors.initials: IF
authors.lastname: Davidson
authors.forename: Thi Bach
authors.initials: TB
authors.lastname: Nga Ly-Hartig
authors.forename: Jan
authors.initials: J
authors.lastname: Ellenberg
authors.forename: Iain W
authors.initials: IW
authors.lastname: Mattaj
mesh_terms: D000595:Amino Acid Sequence; D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D006367:HeLa Cells; D006801:Humans; D034921:Lamin Type B / Q000235:genetics / Q000378:metabolism*; D050356:Lipid Metabolism / Q000502:physiology*; D008938:Mitosis / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D009930:Organic Chemicals / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction
chemical_list: D034921:Lamin Type B; D009687:Nuclear Proteins; D009930:Organic Chemicals; C088310:lipine; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha; D016203:CDC2 Protein Kinase