Myogenin controls via AKAP6 non-centrosomal microtubule-organizing center formation at the nuclear envelope
Non-centrosomal microtubule-organizing centers (MTOCs) 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 nucl...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2021-10-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/65672 |
| _version_ | 1828375508538097664 |
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| author | Robert Becker Silvia Vergarajauregui Florian Billing Maria Sharkova Eleonora Lippolis Kamel Mamchaoui Fulvia Ferrazzi Felix B Engel |
| author_facet | Robert Becker Silvia Vergarajauregui Florian Billing Maria Sharkova Eleonora Lippolis Kamel Mamchaoui Fulvia Ferrazzi Felix B Engel |
| author_sort | Robert Becker |
| collection | DOAJ |
| description | Non-centrosomal microtubule-organizing centers (MTOCs) 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. |
| first_indexed | 2024-04-14T07:48:21Z |
| format | Article |
| id | doaj.art-d9441490c18344098f6e6fe8eafb87b5 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:48:21Z |
| publishDate | 2021-10-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-d9441490c18344098f6e6fe8eafb87b52022-12-22T02:05:17ZengeLife Sciences Publications LtdeLife2050-084X2021-10-011010.7554/eLife.65672Myogenin controls via AKAP6 non-centrosomal microtubule-organizing center formation at the nuclear envelopeRobert Becker0https://orcid.org/0000-0001-7615-9390Silvia Vergarajauregui1https://orcid.org/0000-0002-9247-6123Florian Billing2https://orcid.org/0000-0002-3874-9012Maria Sharkova3Eleonora Lippolis4Kamel Mamchaoui5Fulvia Ferrazzi6https://orcid.org/0000-0003-4011-4638Felix B Engel7https://orcid.org/0000-0003-2605-3429Experimental Renal and Cardiovascular Research, Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, GermanyExperimental Renal and Cardiovascular Research, Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, GermanyExperimental Renal and Cardiovascular Research, Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, GermanyExperimental Renal and Cardiovascular Research, Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, GermanyInstitute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanySorbonne Universités UPMC Université Paris 06, INSERM U974, CNRS FRE3617, Center for Research in Myology, GH Pitié Salpêtrière, 47 Boulevard de l’Hôpital, Paris, FranceInstitute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany; Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany; Institute of Pathology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, GermanyExperimental Renal and Cardiovascular Research, Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany; Muscle Research Center Erlangen (MURCE), Erlangen, GermanyNon-centrosomal microtubule-organizing centers (MTOCs) 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.https://elifesciences.org/articles/65672centrosomeMTOCmyogeninmicrotubulesmuscle differentiationAKAP6 |
| spellingShingle | Robert Becker Silvia Vergarajauregui Florian Billing Maria Sharkova Eleonora Lippolis Kamel Mamchaoui Fulvia Ferrazzi Felix B Engel Myogenin controls via AKAP6 non-centrosomal microtubule-organizing center formation at the nuclear envelope eLife centrosome MTOC myogenin microtubules muscle differentiation AKAP6 |
| title | Myogenin controls via AKAP6 non-centrosomal microtubule-organizing center formation at the nuclear envelope |
| title_full | Myogenin controls via AKAP6 non-centrosomal microtubule-organizing center formation at the nuclear envelope |
| title_fullStr | Myogenin controls via AKAP6 non-centrosomal microtubule-organizing center formation at the nuclear envelope |
| title_full_unstemmed | Myogenin controls via AKAP6 non-centrosomal microtubule-organizing center formation at the nuclear envelope |
| title_short | Myogenin controls via AKAP6 non-centrosomal microtubule-organizing center formation at the nuclear envelope |
| title_sort | myogenin controls via akap6 non centrosomal microtubule organizing center formation at the nuclear envelope |
| topic | centrosome MTOC myogenin microtubules muscle differentiation AKAP6 |
| url | https://elifesciences.org/articles/65672 |
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