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Super-resolution microscopy reveals a preformed NEMO lattice structure that is collapsed in incontinentia pigmenti

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  • Janine Scholefield

    (Faculty of Health Sciences, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Anzio Road, Observatory, Cape Town, Western Cape 7925, South Africa
    Gene Expression and Biophysics Group, CSIR Synthetic Biology ERA)

  • Ricardo Henriques

    (Quantitative Imaging and Nanobiophysics Group, University College London)

  • Anca F. Savulescu

    (Faculty of Health Sciences, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Anzio Road, Observatory, Cape Town, Western Cape 7925, South Africa
    Gene Expression and Biophysics Group, CSIR Synthetic Biology ERA)

  • Elisabeth Fontan

    (Chemogenomic and Biological Screening Core Facility, Institut Pasteur, Center for Innovation and Technological Research (Citech))

  • Alix Boucharlat

    (Chemogenomic and Biological Screening Core Facility, Institut Pasteur, Center for Innovation and Technological Research (Citech))

  • Emmanuel Laplantine

    (Laboratory of Signaling and Pathogenesis, CNRS, UMR 3691, Institut Pasteur)

  • Asma Smahi

    (INSERM U1163-Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Hôpital Necker-Enfants Malades)

  • Alain Israël

    (Laboratory of Signaling and Pathogenesis, CNRS, UMR 3691, Institut Pasteur)

  • Fabrice Agou

    (Chemogenomic and Biological Screening Core Facility, Institut Pasteur, Center for Innovation and Technological Research (Citech))

  • Musa M. Mhlanga

    (Faculty of Health Sciences, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Anzio Road, Observatory, Cape Town, Western Cape 7925, South Africa
    Gene Expression and Biophysics Group, CSIR Synthetic Biology ERA
    Faculdade de Medicina, Gene Expression and Biophysics Unit, Instituto de Medicina Molecular, Universidade de Lisboa)

Abstract

The NF-κB pathway has critical roles in cancer, immunity and inflammatory responses. Understanding the mechanism(s) by which mutations in genes involved in the pathway cause disease has provided valuable insight into its regulation, yet many aspects remain unexplained. Several lines of evidence have led to the hypothesis that the regulatory/sensor protein NEMO acts as a biological binary switch. This hypothesis depends on the formation of a higher-order structure, which has yet to be identified using traditional molecular techniques. Here we use super-resolution microscopy to reveal the existence of higher-order NEMO lattice structures dependent on the presence of polyubiquitin chains before NF-κB activation. Such structures may permit proximity-based trans-autophosphorylation, leading to cooperative activation of the signalling cascade. We further show that NF-κB activation results in modification of these structures. Finally, we demonstrate that these structures are abrogated in cells derived from incontinentia pigmenti patients.

Suggested Citation

  • Janine Scholefield & Ricardo Henriques & Anca F. Savulescu & Elisabeth Fontan & Alix Boucharlat & Emmanuel Laplantine & Asma Smahi & Alain Israël & Fabrice Agou & Musa M. Mhlanga, 2016. "Super-resolution microscopy reveals a preformed NEMO lattice structure that is collapsed in incontinentia pigmenti," Nature Communications, Nature, vol. 7(1), pages 1-13, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12629
    DOI: 10.1038/ncomms12629
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