Myogenin controls via AKAP6 non-centrosomal microtubule organizing center formation at the nuclear envelope
- Friedrich-Alexander-Universität Erlangen-Nürnberg, Germany
- Sorbonne Universités, France
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.
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Transcription Factor Binding Sites by ChIP-seq from ENCODE/CaltechGene Expression Omnibus (GEO) GSE36024.
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Transcriptome changes during the differentiation of myoblasts into myotubesGene Expression Omnibus (GEO) GSE84158.
Article and author information
Author details
Silvia Vergarajauregui
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
- Jens Lüders, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST), Spain
Version history
- Preprint posted: December 11, 2020 (view preprint)
- Received: December 11, 2020
- Accepted: October 1, 2021
- Accepted Manuscript published: October 4, 2021 (version 1)
- Version of Record published: October 18, 2021 (version 2)
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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Myogenin controls via AKAP6 non-centrosomal microtubule organizing center formation at the nuclear envelope
eLife 10:e65672.
https://doi.org/10.7554/eLife.65672
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