Mitotic lamin disassembly is triggered by lipid-mediated signaling

J Cell Biol. 2012 Sep 17;198(6):981-90. doi: 10.1083/jcb.201205103.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • CDC2 Protein Kinase / genetics
  • CDC2 Protein Kinase / metabolism
  • Cell Line
  • HeLa Cells
  • Humans
  • Lamin Type B / genetics
  • Lamin Type B / metabolism*
  • Lipid Metabolism / physiology*
  • Mitosis / genetics
  • Mitosis / physiology*
  • Molecular Sequence Data
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Organic Chemicals / metabolism
  • Phosphorylation
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism
  • Protein Kinase C beta
  • Protein Kinase C-alpha / genetics
  • Protein Kinase C-alpha / metabolism
  • RNA Interference
  • Signal Transduction

Substances

  • Lamin Type B
  • Nuclear Proteins
  • Organic Chemicals
  • lamin B1
  • lipine
  • Protein Kinase C
  • Protein Kinase C beta
  • Protein Kinase C-alpha
  • CDC2 Protein Kinase