Functional diversity of LAP2alpha and LAP2beta in postmitotic chromosome association is caused by an alpha-specific nuclear targeting domain

EMBO J. 1999 Nov 15;18(22):6370-84. doi: 10.1093/emboj/18.22.6370.

Abstract

Lamina-associated polypeptide 2alpha (LAP2alpha) is a non-membrane-bound isoform of the LAP2 family implicated in nuclear structure organization. We show that during postmitotic nuclear assembly LAP2alpha associates with chromosomes prior to accumulation of the membrane-bound isoform LAP2beta, although both proteins contain the same putative chromatin interaction domains located in their common N-terminal regions. By transient and stable expression of various N- and C-terminal LAP2alpha deletion mutants in HeLa cells, we identified an approximately 350-amino-acid-long region in the C-terminal alpha-specific domain of the protein that is required for retention of LAP2alpha in interphase nuclei and for association with mitotic chromosomes, while the N-terminal domain seemed to be dispensable for these interactions. In vitro chromosome binding studies using recombinant LAP2alpha mutants revealed that this LAP2alpha-specific 'nuclear targeting domain' was essential and sufficient for association with chromosomes. These data suggested a functional diversity of chromosome binding properties of LAP2 isoforms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • CHO Cells
  • Cell Cycle / physiology*
  • Cell Line
  • Cell Nucleus / metabolism*
  • Chromosomes / metabolism*
  • Cricetinae
  • DNA-Binding Proteins*
  • HeLa Cells
  • Humans
  • Interphase
  • Membrane Proteins / chemistry*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Metaphase
  • Mitosis
  • Mutagenesis
  • Nuclear Proteins / chemistry*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Isoforms / chemistry
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Rats
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Sequence Deletion
  • Transfection

Substances

  • DNA-Binding Proteins
  • Membrane Proteins
  • Nuclear Proteins
  • Protein Isoforms
  • Recombinant Proteins
  • lamina-associated polypeptide 2