LAP2alpha maintains a mobile and low assembly state of A-type lamins in the nuclear interior
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.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Cell Biology
Dynamic interactions between gut mucosal cells and the external environment are essential to maintain gut homeostasis. Enterochromaffin (EC) cells transduce both chemical and mechanical signals and produce 5-hydroxytryptamine to mediate disparate physiological responses. However, the molecular and cellular basis for functional diversity of ECs remains to be adequately defined. Here, we integrated single-cell transcriptomics with spatial image analysis to identify 14 EC clusters that are topographically organized along the gut. Subtypes predicted to be sensitive to the chemical environment and mechanical forces were identified that express distinct transcription factors and hormones. A Piezo2+ population in the distal colon was endowed with a distinctive neuronal signature. Using a combination of genetic, chemogenetic, and pharmacological approaches, we demonstrated Piezo2+ ECs are required for normal colon motility. Our study constructs a molecular map for ECs and offers a framework for deconvoluting EC cells with pleiotropic functions.
-
- Cell Biology
- Developmental Biology
A study in mice reveals key interactions between proteins involved in fibroblast growth factor signaling and how they contribute to distinct stages of eye lens development.