Journal Article

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

Knapp, Christian, Zier, Elisabeth, Naetar, Nana, Georgiou, Konstantina, Fichtinger, Petra, Foisner, Roland, Bronshtein, Irena, Dechat, Thomas, Garini, Yuval

2021

Overview

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.

• Publisher: eLife Science Publications, Ltd,eLife Sciences Publications Ltd,eLife Sciences Publications, Ltd
• Subject: Amino acids / Animals / Antibodies / assembly / Cell Biology / Cell Line / Cell Nucleus - metabolism / DNA-Binding Proteins - genetics / DNA-Binding Proteins - metabolism / Filaments / Gene expression / lamin dynamics / lamin phosphorylation / Lamin Type A - genetics / Lamin Type A - metabolism / lamin-associated polypeptide 2 / Lamins / lamins in nuclear interior / Localization / Membrane Proteins - genetics / Membrane Proteins - metabolism / Mice / nuclear lamins / Phosphorylation / Proteins / Stem cells / Tomography / Viral antibodies