LAP2alpha Maintains a Mobile and Low Assembly State of A-type Lamins in the Nuclear Interior

Overview

Journal Elife

Specialty Biology

Date 2021 Feb 19

PMID 33605210

Citations 19

Authors

Nana Naetar

Konstantina Georgiou

Christian Knapp

Irena Bronshtein

Elisabeth Zier

Petra Fichtinger

Thomas Dechat

Yuval Garini

Roland Foisner

Affiliations

Soon will be listed here.

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 (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.

Citing Articles

Genetically Encoded Fluorescence Resonance Energy Transfer Biosensor for Live-Cell Visualization of Lamin A Phosphorylation at Serine 22.

Liu J, Li Q, Wang J, Qiu J, Zhou J, Peng Q Biomater Res. 2024; 28:0091.

PMID: 39440272 PMC: 11494032. DOI: 10.34133/bmr.0091.

Lamin chromatin binding is modulated by interactions of different LAP2α domains with lamins and chromatin.

Filipczak D, Souchet A, Georgiou K, Foisner R, Naetar N iScience. 2024; 27(10):110869.

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Mouse polyomavirus infection induces lamin reorganisation.

Brustikova K, Ryabchenko B, Zackova S, Sroller V, Forstova J, Hornikova L FEBS J. 2024; 291(23):5133-5155.

PMID: 39288210 PMC: 11616003. DOI: 10.1111/febs.17275.

LAP2alpha facilitates myogenic gene expression by preventing nucleoplasmic lamin A/C from spreading to active chromatin regions.

Ferraioli S, Sarigol F, Prakash C, Filipczak D, Foisner R, Naetar N Nucleic Acids Res. 2024; 52(19):11500-11518.

PMID: 39228367 PMC: 11514464. DOI: 10.1093/nar/gkae752.

Choreography of lamina-associated domains: structure meets dynamics.

Alagna N, Thomas T, Wilson K, Reddy K FEBS Lett. 2023; 597(22):2806-2822.

PMID: 37953467 PMC: 10858991. DOI: 10.1002/1873-3468.14771.

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