1. Cell Biology
  2. Developmental Biology
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Myogenin controls via AKAP6 non-centrosomal microtubule organizing center formation at the nuclear envelope

  1. Robert Becker
  2. Silvia Vergarajauregui
  3. Florian Billing
  4. Maria Sharkova
  5. Eleonora Lippolis
  6. Kamel Mamchaoui
  7. Fulvia Ferrazzi
  8. Felix B Engel  Is a corresponding author
  1. Friedrich-Alexander-Universität Erlangen-Nürnberg, Germany
  2. Sorbonne Universités, France
Research Article
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Cite this article as: eLife 2021;10:e65672 doi: 10.7554/eLife.65672

Abstract

Non-centrosomal microtubule organizing centers (MTOC) are pivotal for the function of multiple cell types, but the processes initiating their formation are unknown. Here, we find that the transcription factor myogenin is required in murine myoblasts for the localization of MTOC proteins to the nuclear envelope. Moreover, myogenin is sufficient in fibroblasts for nuclear envelope MTOC (NE-MTOC) formation and centrosome attenuation. Bioinformatics combined with loss- and gain-of-function experiments identified induction of AKAP6 expression as one central mechanism for myogenin-mediated NE-MTOC formation. Promoter studies indicate that myogenin preferentially induces the transcription of muscle- and NE-MTOC-specific isoforms of Akap6 and Syne1, which encodes nesprin-1α, the NE-MTOC anchor protein in muscle cells. Overexpression of AKAP6β and nesprin-1α was sufficient to recruit endogenous MTOC proteins to the nuclear envelope of myoblasts in the absence of myogenin. Taken together, our results illuminate how mammals transcriptionally control the switch from a centrosomal MTOC to an NE-MTOC and identify AKAP6 as a novel NE-MTOC component in muscle cells.

Data availability

This work is based exclusively on the analysis of previously published data sets.

The following previously published data sets were used

Article and author information

Author details

  1. Robert Becker

    Experimental Renal and Cardiovascular Research, Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7615-9390
  2. Silvia Vergarajauregui

    Experimental Renal and Cardiovascular Research, Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9247-6123
  3. Florian Billing

    Experimental Renal and Cardiovascular Research, Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3874-9012
  4. Maria Sharkova

    Experimental Renal and Cardiovascular Research, Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Eleonora Lippolis

    Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Kamel Mamchaoui

    Center for Research in Myology, Sorbonne Universités, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  7. Fulvia Ferrazzi

    Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4011-4638
  8. Felix B Engel

    Experimental Renal and Cardiovascular Research, Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
    For correspondence
    felix.engel@uk-erlangen.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2605-3429

Funding

Interdisciplinary Center for Clinical Research , Uniklinikum Erlangen (J42)

  • Fulvia Ferrazzi

Friedrich-Alexander-Universität Erlangen-Nürnberg (ELAN-16-01-04-1-Vergarajauregui)

  • Silvia Vergarajauregui

Friedrich-Alexander-Universität Erlangen-Nürnberg (CYDER)

  • Felix B Engel

Deutsche Forschungsgemeinschaft (INST 410/91-1 FUGG)

  • Felix B Engel

Deutsche Forschungsgemeinschaft (EN 453/12-1)

  • Felix B Engel

Research Foundation Medicine at the University Clinic Erlangen

  • Silvia Vergarajauregui
  • Felix B Engel

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Jens Lüders, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST), Spain

Publication history

  1. Received: December 11, 2020
  2. Accepted: October 1, 2021
  3. Accepted Manuscript published: October 4, 2021 (version 1)

Copyright

© 2021, Becker 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.

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