Lap2alpha Maintains A Mobile And Low Assembly State Of A-Type Lamins In The Nuclear Interior

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 (LAP2 alpha). Using antibody labeling, we previously observed a depletion of nucleoplasmic A-type lamins in mouse cells lacking LAP2 alpha. Here, we show that loss of LAP2 alpha 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 LAP2 alpha-independent manner, binding of LAP2 alpha to lamin 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 LAP2 alpha is essential to maintain a mobile lamin A/C pool in the nuclear interior, which is required for proper nuclear functions.