Emerin Self-assembly and Nucleoskeletal Coupling Regulate Nuclear Envelope Mechanics Against Stress

Overview

Journal J Cell Sci

Specialty Cell Biology

Date 2022 Feb 18

PMID 35178558

Authors

Anthony Fernandez

Markville Bautista

Liying Wu

Fabien Pinaud

Affiliations

Soon will be listed here.

Abstract

Emerin is an integral nuclear envelope protein that participates in the maintenance of nuclear shape. When mutated or absent, emerin causes X-linked Emery-Dreifuss muscular dystrophy (EDMD). To understand how emerin takes part in molecular --scaffolding at the nuclear envelope and helps protect the nucleus against mechanical stress, we established its nanoscale organization using single-molecule tracking and super-resolution microscopy. We show that emerin monomers form localized oligomeric nanoclusters stabilized by both lamin A/C and the SUN1-containing linker of nucleoskeleton and cytoskeleton (LINC) complex. Interactions of emerin with nuclear actin and BAF (also known as BANF1) additionally modulate its membrane mobility and its ability to oligomerize. In nuclei subjected to mechanical challenges, the mechanotransduction functions of emerin are coupled to changes in its oligomeric state, and the incremental self-assembly of emerin determines nuclear shape adaptation against mechanical forces. We also show that the abnormal nuclear envelope deformations induced by EDMD emerin mutants stem from improper formation of lamin A/C and LINC complex-stabilized emerin oligomers. These findings place emerin at the center of the molecular processes that regulate nuclear shape remodeling in response to mechanical challenges.

Citing Articles

C-terminal tagging, transmembrane domain hydrophobicity, and an ER retention motif influence the secretory trafficking of the inner nuclear membrane protein emerin.

Mella J, Volk R, Zaro B, Buchwalter A bioRxiv. 2025; .

PMID: 39896633 PMC: 11785080. DOI: 10.1101/2025.01.19.633811.

At the nucleus of cancer: how the nuclear envelope controls tumor progression.

Paganelli F, Poli A, Truocchio S, Martelli A, Palumbo C, Lattanzi G MedComm (2020). 2025; 6(2):e70073.

PMID: 39866838 PMC: 11758262. DOI: 10.1002/mco2.70073.

Measuring age-dependent viscoelasticity of organelles, cells and organisms with time-shared optical tweezer microrheology.

Catala-Castro F, Ortiz-Vasquez S, Martinez-Fernandez C, Pezzano F, Garcia-Cabau C, Fernandez-Campo M Nat Nanotechnol. 2025; .

PMID: 39747604 DOI: 10.1038/s41565-024-01830-y.

N-terminal tags impair the ability of lamin A to provide structural support to the nucleus.

Odell J, Lammerding J J Cell Sci. 2024; 137(16).

PMID: 39092499 PMC: 11361635. DOI: 10.1242/jcs.262207.

Native lamin A/C proteomes and novel partners from heart and skeletal muscle in a mouse chronic inflammation model of human frailty.

Elzamzami F, Samal A, Arun A, Dharmaraj T, Prasad N, Rendon-Jonguitud A Front Cell Dev Biol. 2023; 11:1240285.

PMID: 37936983 PMC: 10626543. DOI: 10.3389/fcell.2023.1240285.

References

Hirano Y, Segawa M, Ouchi F, Yamakawa Y, Furukawa K, Takeyasu K . Dissociation of emerin from barrier-to-autointegration factor is regulated through mitotic phosphorylation of emerin in a xenopus egg cell-free system. J Biol Chem. 2005; 280(48):39925-33. DOI: 10.1074/jbc.M503214200. View

Serge A, Bertaux N, Rigneault H, Marguet D . Dynamic multiple-target tracing to probe spatiotemporal cartography of cell membranes. Nat Methods. 2008; 5(8):687-94. DOI: 10.1038/nmeth.1233. View

Fernandez A, Bautista M, Stanciauskas R, Chung T, Pinaud F . Cell-Shaping Micropatterns for Quantitative Super-Resolution Microscopy Imaging of Membrane Mechanosensing Proteins. ACS Appl Mater Interfaces. 2017; 9(33):27575-27586. DOI: 10.1021/acsami.7b09743. View

Kirby T, Lammerding J . Emerging views of the nucleus as a cellular mechanosensor. Nat Cell Biol. 2018; 20(4):373-381. PMC: 6440800. DOI: 10.1038/s41556-018-0038-y. View

Bengtsson L, Wilson K . Multiple and surprising new functions for emerin, a nuclear membrane protein. Curr Opin Cell Biol. 2004; 16(1):73-9. DOI: 10.1016/j.ceb.2003.11.012. View

Cui Y, Hameed F, Yang B, Lee K, Pan C, Park S . Cyclic stretching of soft substrates induces spreading and growth. Nat Commun. 2015; 6:6333. PMC: 4346610. DOI: 10.1038/ncomms7333. View

Soumpasis D . Theoretical analysis of fluorescence photobleaching recovery experiments. Biophys J. 1983; 41(1):95-7. PMC: 1329018. DOI: 10.1016/S0006-3495(83)84410-5. View

Baarlink C, Plessner M, Sherrard A, Morita K, Misu S, Virant D . A transient pool of nuclear F-actin at mitotic exit controls chromatin organization. Nat Cell Biol. 2017; 19(12):1389-1399. DOI: 10.1038/ncb3641. View

Roberts R, Sutherland-Smith A, Wheeler M, Jensen O, Emerson L, Spiliotis I . The Emery-Dreifuss muscular dystrophy associated-protein emerin is phosphorylated on serine 49 by protein kinase A. FEBS J. 2006; 273(19):4562-75. DOI: 10.1111/j.1742-4658.2006.05464.x. View

10.

Ostlund C, Ellenberg J, Hallberg E, Lippincott-Schwartz J, Worman H . Intracellular trafficking of emerin, the Emery-Dreifuss muscular dystrophy protein. J Cell Sci. 1999; 112 ( Pt 11):1709-19. DOI: 10.1242/jcs.112.11.1709. View

11.

Lee K, Haraguchi T, Lee R, Koujin T, Hiraoka Y, Wilson K . Distinct functional domains in emerin bind lamin A and DNA-bridging protein BAF. J Cell Sci. 2002; 114(Pt 24):4567-73. DOI: 10.1242/jcs.114.24.4567. View

12.

Crisp M, Liu Q, Roux K, Rattner J, Shanahan C, Burke B . Coupling of the nucleus and cytoplasm: role of the LINC complex. J Cell Biol. 2005; 172(1):41-53. PMC: 2063530. DOI: 10.1083/jcb.200509124. View

13.

Jahed Z, Fadavi D, Vu U, Asgari E, Luxton G, Mofrad M . Molecular Insights into the Mechanisms of SUN1 Oligomerization in the Nuclear Envelope. Biophys J. 2018; 114(5):1190-1203. PMC: 5883562. DOI: 10.1016/j.bpj.2018.01.015. View

14.

Tokunaga M, Imamoto N, Sakata-Sogawa K . Highly inclined thin illumination enables clear single-molecule imaging in cells. Nat Methods. 2008; 5(2):159-61. DOI: 10.1038/nmeth1171. View

15.

Herrada I, Samson C, Velours C, Renault L, Ostlund C, Chervy P . Muscular Dystrophy Mutations Impair the Nuclear Envelope Emerin Self-assembly Properties. ACS Chem Biol. 2015; 10(12):2733-42. PMC: 4869717. DOI: 10.1021/acschembio.5b00648. View

16.

Lagardere M, Chamma I, Bouilhol E, Nikolski M, Thoumine O . FluoSim: simulator of single molecule dynamics for fluorescence live-cell and super-resolution imaging of membrane proteins. Sci Rep. 2020; 10(1):19954. PMC: 7672080. DOI: 10.1038/s41598-020-75814-y. View

17.

Mortensen K, Churchman L, Spudich J, Flyvbjerg H . Optimized localization analysis for single-molecule tracking and super-resolution microscopy. Nat Methods. 2010; 7(5):377-81. PMC: 3127582. DOI: 10.1038/nmeth.1447. View

18.

Fidzianska A, Hausmanowa-Petrusewicz I . Architectural abnormalities in muscle nuclei. Ultrastructural differences between X-linked and autosomal dominant forms of EDMD. J Neurol Sci. 2003; 210(1-2):47-51. DOI: 10.1016/s0022-510x(03)00012-1. View

19.

Haraguchi T, Kojidani T, Koujin T, Shimi T, Osakada H, Mori C . Live cell imaging and electron microscopy reveal dynamic processes of BAF-directed nuclear envelope assembly. J Cell Sci. 2008; 121(Pt 15):2540-54. DOI: 10.1242/jcs.033597. View

20.

Stoynova L, Solorzano R, Collins E . Generation of large deletion mutants from plasmid DNA. Biotechniques. 2004; 36(3):402-4, 406. DOI: 10.2144/04363BM05. View