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The Golgi apparatus is the main microtubule-organizing center in differentiating skeletal muscle cells

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Abstract

Studies in differentiating skeletal muscle cells in vitro have revealed that the microtubule-organizing center shifts from the centrosome to the perinuclear sites. As the Golgi apparatus surrounds the nucleus in a myotube, it is unclear whether microtubules are nucleated at the nuclear envelope or at the surrounding Golgi apparatus. In this study, we investigated the positional relationship between the microtubule nucleating sites and the Golgi apparatus in C2C12 myotubes and in primary cultured mouse skeletal myotubes. We focused on gaps in the perinuclear Golgi apparatus where the nuclear envelope was not covered with the Golgi apparatus. In microtubule regrowth assay, microtubule regrowth after cold-nocodazole depolymerization of preexisting microtubules was not found at the gap of the perinuclear Golgi apparatus. Most of the microtubule regrowth was detected at the CDK5RAP2 (CDK5 regulatory subunit-associated protein 2)-rich spots on the perinuclear Golgi apparatus. Disruption of the perinuclear Golgi apparatus with brefeldin A treatment eliminated the perinuclear microtubule regrowth. The Golgi apparatus of undifferentiated myoblasts and those at the cytoplasm of myotubes were also the microtubule nucleating sites. From these observations, we concluded that most of the perinuclear microtubule nucleation occurs on the Golgi apparatus surrounding the nucleus.

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Availability of data and material

The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

  • Becker R, Leone M, Engel FB (2020) Microtubule organization in striated muscle cells. Cells 9:1395. https://doi.org/10.3390/cells9061395

    Article  CAS  PubMed Central  Google Scholar 

  • Bugnard E, Zaal KJ, Ralston E (2005) Reorganization of microtubule nucleation during muscle differentiation. Cell Motil Cytoskelet 60:1–13

    Article  Google Scholar 

  • Ellis JA (2006) Emery-Dreifuss muscular dystrophy at the nuclear envelope: 10 years on. Cell Mol Life Sci 63:2702–2709. https://doi.org/10.1007/s00018-006-6247-8

    Article  CAS  PubMed  Google Scholar 

  • Ervasti JM (2003) Costameres: the Achilles’ heel of Herculean muscle. J Biol Chem 278:13591–13594

    Article  CAS  Google Scholar 

  • Espigat-Georger A, Dyachuk V, Chemin C, Emorine L, Merdes A (2016) Nuclear alignment in myotubes requires centrosome proteins recruited by nesprin-1. J Cell Sci 129:4227–4237

    CAS  PubMed  Google Scholar 

  • Gimpel P, Lee YL, Sobota RM, Calvi A, Koullourou V, Patel R, Mamchaoui K, Nedelec F, Shackleton S, Schmoranzer J, Burke B, Cadot B, Gomes ER (2017) Nesprin-1alpha-dependent microtubule nucleation from the nuclear envelope via Akap450 is necessary for nuclear positioning in muscle cells. Currentbiology 27:2999–3009. https://doi.org/10.1016/j.cub.2017.08.031

    Article  CAS  Google Scholar 

  • Khairallah RJ, Shi G, Sbrana F, Prosser BL, Borroto C, Mazaitis MJ, Hoffman EP, Mahurkar A, Sachs F, Sun Y, Chen YW, Raiteri R, Lederer WJ, Dorsey SG, Ward CW (2012) Microtubules underlie dysfunction in duchenne muscular dystrophy. Science Signaling 5:ra56

    Article  Google Scholar 

  • Liu P, Zupa E, Neuner A, Bohler A, Loerke J, Flemming D, Ruppert T, Rudack T, Peter C, Spahn C, Gruss OJ, Pfeffer S, Schiebel E (2020) Insights into the assembly and activation of the microtubule nucleator gamma-TuRC. Nature 578:467–471

    Article  CAS  Google Scholar 

  • Nishita M, Satake T, Minami Y, Suzuki A (2017) Regulatory mechanisms and cellular functions of non-centrosomal microtubules. J Biochem 162:1–10

    Article  CAS  Google Scholar 

  • Oddoux S, Zaal KJ, Tate V, Kenea A, Nandkeolyar SA, Reid E, Liu W, Ralston E (2013) Microtubules that form the stationary lattice of muscle fibers are dynamic and nucleated at Golgi elements. J Cell Biol 203:205–213

    Article  CAS  Google Scholar 

  • Oddoux S, Randazzo D, Kenea A, Alonso B, Zaal KJM, Ralston E (2019) Misplaced Golgi elements produce randomly oriented microtubules and aberrant cortical arrays of microtubules in dystrophic skeletal muscle fibers. Front Cell Dev Biol 7:176

    Article  Google Scholar 

  • Prins KW, Humston JL, Mehta A, Tate V, Ralston E, Ervasti JM (2009) Dystrophin is a microtubule-associated protein. J Cell Biol 186:363–369

    Article  CAS  Google Scholar 

  • Ralston E, Lu Z, Ploug T (1999) The organization of the Golgi complex and microtubules in skeletal muscle is fiber type-dependent. J Neurosci: off J Soci Neurosci 19:10694–10705

    Article  CAS  Google Scholar 

  • Remy MH, Merdes A, Gregory-Pauron L (2013) Assembly of gamma-tubulin ring complexes: implications for cell biology and disease. Prog Mol Biol Transl Sci 117:511–530

    Article  CAS  Google Scholar 

  • Roman W, Gomes ER (2018) Nuclear positioning in skeletal muscle. Semin Cell Dev Biol 82:51–56

    Article  CAS  Google Scholar 

  • Sanders AA, Kaverina I (2015) Nucleation and dynamics of Golgi-derived microtubules. Front Neurosci 9:431

    Article  Google Scholar 

  • Starr DA (2017) Muscle development: nucleating microtubules at the nuclear envelope. Curr Biol: CB 27:R1071–R1073

    Article  CAS  Google Scholar 

  • Tassin AM, Maro B, Bornens M (1985a) Fate of microtubule-organizing centers during myogenesis in vitro. J Cell Biol 100:35–46

    Article  CAS  Google Scholar 

  • Tassin AM, Paintrand M, Berger EG, Bornens M (1985b) The Golgi apparatus remains associated with microtubule organizing centers during myogenesis. J Cell Biol 101:630–638

    Article  CAS  Google Scholar 

  • Vergarajauregui S, Becker R, Steffen U, Sharkova M, Esser T, Petzold J, Billing F, Kapiloff MS, Schett G, Thievessen I, Engel FB (2020) AKAP6 orchestrates the nuclear envelope microtubule-organizing center by linking golgi and nucleus via AKAP9. Elife 9:61669. https://doi.org/10.7554/eLife.61669

    Article  Google Scholar 

  • Wu J, de Heus C, Liu Q, Bouchet BP, Noordstra I, Jiang K, Hua S, Martin M, Yang C, Grigoriev I, Katrukha EA, Altelaar AFM, Hoogenraad CC, Qi RZ, Klumperman J, Akhmanova A (2016) Molecular pathway of microtubule organization at the golgi apparatus. Dev Cell 39:44–60

    Article  CAS  Google Scholar 

  • Yamada M, Hayashi K (2019) Microtubule nucleation in the cytoplasm of developing cortical neurons and its regulation by brain-derived neurotrophic factor. Cytoskeleton 76:339–345

    Article  CAS  Google Scholar 

  • Yonezawa S, Shigematsu M, Hirata K, Hayashi K (2015) Loss of gamma-tubulin, GCP-WD/NEDD1 and CDK5RAP2 from the centrosome of neurons in developing mouse cerebral and cerebellar cortex. Acta Histochem Cytochem 48:145–152

    Article  CAS  Google Scholar 

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Funding

This study was funded by the Japanese Society for the Promotion of Science (JSPS KAKENHI grant number JP17K07083).

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KH designed and supervised the study. YI performed the analysis on C2C12 cells, and MM performed the analysis on primary cultured muscle cells. All authors read and approved the final manuscript.

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Correspondence to Kensuke Hayashi.

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The authors declare no potential conflicts of interest with respect to the research, authorship and publication of this article.

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Ide, K., Muko, M. & Hayashi, K. The Golgi apparatus is the main microtubule-organizing center in differentiating skeletal muscle cells. Histochem Cell Biol 156, 273–281 (2021). https://doi.org/10.1007/s00418-021-01999-6

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