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

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.