LAP2alpha maintains a mobile and low assembly state of A-type lamins in the nuclear interior
- Medical University Vienna, Austria
- Bar Ilan University, Israel
Abstract
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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 2G-H, Figure 4A-B and Figure 6A
Article and author information
Author details
Funding
Austrian Science Fund (P26492-B20,P29713-B28,P32512-B)
- Roland Foisner
Austrian Academy of Sciences (APART 11657)
- Nana Naetar
Israel Science Foundation (ISF grant 1219/17)
- Irena Bronshtein
- Yuval Garini
European Cooperation in Science and Technology (COST-STSM-BM1002-8698,COST-STSM-BM1002-11436)
- Thomas Dechat
European Molecular Biology Organization (ASTF 316-2011)
- Thomas Dechat
S Grosskopf Grant
- Irena Bronshtein
- Yuval Garini
Austrian Academy of Sciences (ÖAW DOC 25725)
- Konstantina Georgiou
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2021, Naetar et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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LAP2alpha maintains a mobile and low assembly state of A-type lamins in the nuclear interior
eLife 10:e63476.
https://doi.org/10.7554/eLife.63476
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