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Mena regulates nesprin-2 to control actin–nuclear lamina associations, trans-nuclear membrane signalling and gene expression

Author

Listed:
  • Frederic Li Mow Chee

    (University of Edinburgh)

  • Bruno Beernaert

    (University of Edinburgh
    University of Oxford)

  • Billie G. C. Griffith

    (University of Edinburgh)

  • Alexander E. P. Loftus

    (University of Edinburgh)

  • Yatendra Kumar

    (University of Edinburgh)

  • Jimi C. Wills

    (University of Edinburgh)

  • Martin Lee

    (University of Edinburgh)

  • Jessica Valli

    (Heriot-Watt University)

  • Ann P. Wheeler

    (University of Edinburgh)

  • J. Douglas Armstrong

    (University of Edinburgh)

  • Maddy Parsons

    (King’s College London)

  • Irene M. Leigh

    (University of Dundee
    Queen Mary University of London)

  • Charlotte M. Proby

    (University of Dundee)

  • Alex Kriegsheim

    (University of Edinburgh)

  • Wendy A. Bickmore

    (University of Edinburgh)

  • Margaret C. Frame

    (University of Edinburgh)

  • Adam Byron

    (University of Edinburgh
    University of Manchester, Manchester Academic Health Science Centre)

Abstract

Interactions between cells and the extracellular matrix, mediated by integrin adhesion complexes, play key roles in fundamental cellular processes, including the sensing and transduction of mechanical cues. Here, we investigate systems-level changes in the integrin adhesome in patient-derived cutaneous squamous cell carcinoma cells and identify the actin regulatory protein Mena as a key node in the adhesion complex network. Mena is connected within a subnetwork of actin-binding proteins to the LINC complex component nesprin-2, with which it interacts and co-localises at the nuclear envelope. Moreover, Mena potentiates the interactions of nesprin-2 with the actin cytoskeleton and the nuclear lamina. CRISPR-mediated Mena depletion causes altered nuclear morphology, reduces tyrosine phosphorylation of the nuclear membrane protein emerin and downregulates expression of the immunomodulatory gene PTX3 via the recruitment of its enhancer to the nuclear periphery. We uncover an unexpected role for Mena at the nuclear membrane, where it controls nuclear architecture, chromatin repositioning and gene expression. Our findings identify an adhesion protein that regulates gene transcription via direct signalling across the nuclear envelope.

Suggested Citation

  • Frederic Li Mow Chee & Bruno Beernaert & Billie G. C. Griffith & Alexander E. P. Loftus & Yatendra Kumar & Jimi C. Wills & Martin Lee & Jessica Valli & Ann P. Wheeler & J. Douglas Armstrong & Maddy Pa, 2023. "Mena regulates nesprin-2 to control actin–nuclear lamina associations, trans-nuclear membrane signalling and gene expression," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37021-x
    DOI: 10.1038/s41467-023-37021-x
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    References listed on IDEAS

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    1. Leland H. Hartwell & John J. Hopfield & Stanislas Leibler & Andrew W. Murray, 1999. "From molecular to modular cell biology," Nature, Nature, vol. 402(6761), pages 47-52, December.
    2. Gareth J. Inman & Jun Wang & Ai Nagano & Ludmil B. Alexandrov & Karin J. Purdie & Richard G. Taylor & Victoria Sherwood & Jason Thomson & Sarah Hogan & Lindsay C. Spender & Andrew P. South & Michael S, 2018. "The genomic landscape of cutaneous SCC reveals drivers and a novel azathioprine associated mutational signature," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    3. van Buuren, Stef & Groothuis-Oudshoorn, Karin, 2011. "mice: Multivariate Imputation by Chained Equations in R," Journal of Statistical Software, Foundation for Open Access Statistics, vol. 45(i03).
    4. Marten Postma & Joachim Goedhart, 2019. "PlotsOfData—A web app for visualizing data together with their summaries," PLOS Biology, Public Library of Science, vol. 17(3), pages 1-8, March.
    5. Hawa-Racine Thiam & Pablo Vargas & Nicolas Carpi & Carolina Lage Crespo & Matthew Raab & Emmanuel Terriac & Megan C. King & Jordan Jacobelli & Arthur S. Alberts & Theresia Stradal & Ana-Maria Lennon-D, 2016. "Perinuclear Arp2/3-driven actin polymerization enables nuclear deformation to facilitate cell migration through complex environments," Nature Communications, Nature, vol. 7(1), pages 1-14, April.
    6. Anna Woroniuk & Andrew Porter & Gavin White & Daniel T. Newman & Zoi Diamantopoulou & Thomas Waring & Claire Rooney & Douglas Strathdee & Daniel J. Marston & Klaus M. Hahn & Owen J. Sansom & Tobias Ze, 2018. "STEF/TIAM2-mediated Rac1 activity at the nuclear envelope regulates the perinuclear actin cap," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    7. Lars Guelen & Ludo Pagie & Emilie Brasset & Wouter Meuleman & Marius B. Faza & Wendy Talhout & Bert H. Eussen & Annelies de Klein & Lodewyk Wessels & Wouter de Laat & Bas van Steensel, 2008. "Domain organization of human chromosomes revealed by mapping of nuclear lamina interactions," Nature, Nature, vol. 453(7197), pages 948-951, June.
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