Coordination of kinase and phosphatase activities by Lem4 enables nuclear envelope reassembly during mitosis

Cell. 2012 Jul 6;150(1):122-35. doi: 10.1016/j.cell.2012.04.043.

Abstract

Mitosis in metazoa requires nuclear envelope (NE) disassembly and reassembly. NE disassembly is driven by multiple phosphorylation events. Mitotic phosphorylation of the protein BAF reduces its affinity for chromatin and the LEM family of inner nuclear membrane proteins; loss of this BAF-mediated chromatin-NE link contributes to NE disassembly. BAF must reassociate with chromatin and LEM proteins at mitotic exit to reform the NE; however, how its dephosphorylation is regulated is unknown. Here, we show that the C. elegans protein LEM-4L and its human ortholog Lem4 (also called ANKLE2) are both required for BAF dephosphorylation. They act in part by inhibiting BAF's mitotic kinase, VRK-1, in vivo and in vitro. In addition, Lem4/LEM-4L interacts with PP2A and is required for it to dephosphorylate BAF during mitotic exit. By coordinating VRK-1- and PP2A-mediated signaling on BAF, Lem4/LEM-4L controls postmitotic NE formation in a function conserved from worms to humans.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Caenorhabditis elegans / cytology*
  • Caenorhabditis elegans / enzymology
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / chemistry
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Carrier Proteins / metabolism
  • DNA-Binding Proteins / metabolism
  • HeLa Cells
  • Humans
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism*
  • Mitosis*
  • Mutation
  • Nuclear Envelope / metabolism*
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism*
  • Protein Phosphatase 2 / metabolism*
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*

Substances

  • ANKLE2 protein, human
  • BAF-1 protein, C elegans
  • BANF1 protein, human
  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • DNA-Binding Proteins
  • Lem-4L protein, C elegans
  • Membrane Proteins
  • Nuclear Proteins
  • Protein-Serine-Threonine Kinases
  • VRK-1 protein, C elegans
  • Protein Phosphatase 2