LAP2alpha maintains a mobile and low assembly state of A-type lamins in the nuclear interior

• Main Authors: Nana Naetar, Konstantina Georgiou, Christian Knapp, Irena Bronshtein, Elisabeth Zier, Petra Fichtinger, Thomas Dechat, Yuval Garini, Roland Foisner
• Format: Article
• Language: English
• Published: eLife Sciences Publications Ltd 2021-02-01
• Series: eLife
• Subjects: nuclear lamins; lamins in nuclear interior; lamin-associated polypeptide 2; lamin dynamics; assembly; lamin phosphorylation
• Online Access: https://elifesciences.org/articles/63476

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). Using antibody labeling, we previously observed a depletion of nucleoplasmic A-type lamins in mouse cells lacking LAP2α. Here, we show that loss of LAP2α 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 LAP2α-independent manner, binding of LAP2α 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 LAP2α is essential to maintain a mobile lamin A/C pool in the nuclear interior, which is required for proper nuclear functions.