Functional diversity of LAP2α and LAP2β in postmitotic chromosome association is caused by an α-specific nuclear targeting domain

Abstract

Lamina-associated polypeptide 2α (LAP2α) is a non-membrane-bound isoform of the LAP2 family implicated in nuclear structure organization. We show that during postmitotic nuclear assembly LAP2α associates with chromosomes prior to accumulation of the membrane-bound isoform LAP2β, 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 LAP2α deletion mutants in HeLa cells, we identified an ~350-amino-acid-long region in the C-terminal α-specific domain of the protein that is required for retention of LAP2α 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 LAP2α mutants revealed that this LAP2α-specific 'nuclear targeting domain' was essential and sufficient for association with chromosomes. These data suggested a functional diversity of chromesome binding properties of LAP2 isoforms.