Lamins form stable filaments at the nuclear periphery in metazoans. Unlike B-type lamins, lamins A and C localize also in the nuclear interior, where they interact with lamin-associated polypeptide 2 alpha (LAP2a). Using antibody labeling, we previously observed a depletion of nucleoplasmic A-type lamins in mouse cells lacking LAP2a. Here we show that loss of LAP2a actually causes formation of larger, biochemically stable lamin A/C structures in the nuclear interior that are inaccessible to lamin A/C antibodies. While nucleoplasmic lamin A forms from newly expressed pre-lamin A during processing and from soluble mitotic lamins in a LAP2a-independent manner, binding of LAP2a to lamins A/C during interphase inhibits formation of higher order structures, keeping nucleoplasmic lamin A/C in a mobile state independent of lamin A/C S22 phosphorylation. We propose that LAP2a is essential to maintain a mobile lamin A/C pool in the nuclear interior, which is required for proper nuclear functions.

Lamins form stable filaments at the nuclear periphery in metazoans. Unlike B-type lamins, lamins A and C localize also in the nuclear interior, where they interact with lamin-associated polypeptide 2 alpha (LAP2α). We show that lamin A in the nuclear interior is formed from newly expressed pre-lamin A during processing and from soluble mitotic mature lamins in a LAP2α-independent manner. Binding of LAP2α to lamins A/C in the nuclear interior during interphase inhibits formation of higher order structures of lamin A/C in vitro and in vivo, keeping lamin A/C in a mobile low assembly state independent of lamin A/C S22 phosphorylation. Loss of LAP2α causes formation of larger, less mobile and biochemically stable lamin A/C structures in the nuclear interior, which reduce the mobility of chromatin. We propose that LAP2α is essential to maintain a mobile lamin A/C pool in the nuclear interior, which is required for proper nuclear functions.