Abstract
Myoblast differentiation is a complex process. As myoblasts differentiate into myofibers, they acquire a cell type-specific transcriptional program, irreversibly exit the cell cycle, and dramatically change their morphology. The morphological changes include cell elongation, alignment, and fusion into syncytial myofibers. Several lines of evidence suggest that these events may be co-regulated. However, the mechanisms that coordinate major alterations in a cell’s transcriptome and its shape are not well understood. Muscle-specific transcription is controlled by proteins of the MyoD family, transcription factors whose activity is regulated by specific signal transduction pathways, including the p38 MAP kinase pathway. In a search for genes that might play a role in linking myogenic signal transduction, cytoskeletal regulation, and myoblast differentiation, Dbn1 (encoding the actin regulator drebrin) was identified. Dbn1 expression is induced during myoblast differentiation, in a p38 MAP kinase- and MyoD- dependent manner. RNAi-mediated depletion of drebrin, or treatment with a chemical drebrin inhibitor, resulted in a similar phenotype in myoblasts: defective differentiation, with low levels of early and late differentiation markers and inefficient production of myofibers. Drebrin localizes at sites of cell-cell contact and cell extensions, locations that are also enriched for F-actin. Drebrin may be important in linking transcriptional and morphological aspects of myoblast differentiation.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Abramovici H, Gee SH (2007) Morphological changes and spatial regulation of diacylglycerol kinase-zeta, syntrophins, and Rac1 during myoblast fusion. Cell Motil Cytoskeleton 64:549–567
de Angelis L, Zhao J, Andreucci JJ, Olson EN, Cossu G, McDermott JC (2005) Regulation of vertebrate myotome development by the p38 MAP kinase-MEF2 signaling pathway. Dev Biol 283:171–179
Bae GU, Gaio U, Yang YJ, Lee HJ, Kang JS, Krauss RS (2008) Regulation of myoblast motility and fusion by the CXCR4-associated sialomucin, CD164. J Biol Chem 283:8301–8309
Bergstrom DA, Penn BH, Strand A, Perry RL, Rudnicki MA, Tapscott SJ (2002) Promoter-specific regulation of MyoD binding and signal transduction cooperate to pattern gene expression. Mol Cell 9:587–600
Biressi S, Molinaro M, Cossu G (2007) Cellular heterogeneity during vertebrate skeletal muscle development. Dev Biol 308:281–293
Briata P, Forcales SV, Ponassi M, Corte G, Chen CY, Karin M, Puri PL, Gherzi R (2005) p38-dependent phosphorylation of the mRNA decay-promoting factor KSRP controls the stability of select myogenic transcripts. Mol Cell 20:891–903
Butkevich E, Bodensiek K, Fakhri N, von Roden K, Schaap IAT, Majoul I, Schmidt CF, Klopfenstein DR (2015) Drebrin-like protein DBN-1 is a sarcomere component that stabilizes actin filaments during muscle contraction. Nat Commun 6:7523. doi:10.1038/ncomms8523
Chang NC, Rudnicki MA (2014) Satellite cells: the architects of skeletal muscle. Curr Top Dev Biol 107:161–181
Chang W, Webster DR, Salam AA, Gruber D, Prasad A, Eiserich JP, Bulinski JC (2002) Alteration of the C-terminal amino acid of tubulin specifically inhibits myogenic differentiation. J Biol Chem 277:30690–30698
Charge SB, Rudnicki MA (2004) Cellular and molecular regulation of muscle regeneration. Physiol Rev 84:209–238
Chen EH, Grote E, Mohler W, Vignery A (2007a) Cell-cell fusion. FEBS Lett 581:2181–2193
Chen SE, Jin B, Li YP (2007b) TNF-α regulates myogenesis and muscle regeneration by activating p38 MAPK. Am J Phys Cell Physiol 292:C1660–C1671
Conti FJ, Monkley SJ, Wood MR, Critchley DR, Müller U (2009) Talin 1 and 2 are required for myoblast fusion, sarcomere assembly and the maintenance of myotendinous junctions. Development 136:3597–3606
Cuenda A, Cohen P (1999) Stress-activated protein kinase-2/p38 and a rapamycin- sensitive pathway are required for C2C12 myogenesis. J Biol Chem 274:4341–4346
Cuenda A, Rousseau S (2007) p38 MAP-kinases pathway regulation, function and role in human diseases. Biochim Biophys Acta 1773:1358–1375
Forcales SV, Albini S, Giordani L, Malecova B, Cignolo L, Chernov A, Coutinho P, Saccone V, Consalvi S, Williams R et al (2012) Signal-dependent incorporation of MyoD–BAF60c into Brg1-based SWI/SNF chromatin-remodelling complex. EMBO J 31:301–316
Geraldo S, Khanzada UK, Parsons M, Chilton JK, Gordon-Weeks PR (2008) Targeting of the F-actin-binding protein drebrin by the microtubule plus-tip protein EB3 is required for neuritogenesis. Nat Cell Biol 10:1181–1189
Griffin CA, Apponi LH, Long KK, Pavlath GK (2010) Chemokine expression and control of muscle cell migration during myogenesis. J Cell Sci 123:3052–3060
Gros J, Manceau M, Thomé V, Marcelle C (2005) A common somitic origin for embryonic muscle progenitors and satellite cells. Nature 435:954–958
Guasconi V, Puri PL (2009) Chromatin: the interface between extrinsic cues and the epigenetic regulation of muscle regeneration. Trends Cell Biol 19:286–294
Han J-W, Lee H-J, Bae G-U, Kang J-S (2011) Promyogenic function of Integrin/FAK signaling is mediated by Cdo, Cdc42 and MyoD. Cell Signal 23(7):1162–1169
Horsley V, Pavlath GK (2002) NFAT: ubiquitous regulator of cell differentiation and adaptation. J Cell Biol 156:771–774
Jansen KM, Pavlath GK (2008) Molecular control of mammalian myoblast fusion. Methods Mol Biol 475:115–133
Jiang BH, Zheng JZ, Vogt PK (1998) An essential role of phosphatidylinositol 3- kinase in myogenic differentiation. Proc Natl Acad Sci U S A 95:14179–14183
Jiang BH, Aoki M, Zheng JZ, Li J, Vogt PK (1999) Myogenic signaling of phosphatidylinositol 3-kinase requires the serine-threonine kinase Akt/protein kinase B. Proc Natl Acad Sci U S A 96:2077–2081
Kang J-S, Bae G-U, Yi M-J, Yang Y-J, Oh J-E, Takaesu G, Zhou YT, Low BC, Krauss RS (2008) A Cdo/Bnip-2/Cdc42 signaling pathway regulates p38α/β MAPK activity and myogenic differentiation. J Cell Biol 182:497–507
Kassar-Duchossoy L, Giacone E, Gayraud-Morel B, Jory A, Gomès D, Tajbakhsh S (2005) Pax3/Pax7 mark a novel population of primitive myogenic cells during development. Genes Dev 19:1426–1431
Kim SJ, Kim S, Shin H, Uhm CS (2008) Intercellular interaction observed by atomic force microscopy. Ultramicroscopy 108:1148–1151
Laurin M, Fradet N, Blangy A, Hall A, Vuori K, Côté JF (2008) The atypical Rac activator Dock180 (Dock1) regulates myoblast fusion in vivo. Proc Natl Acad Sci U S A 105:15446–15451
Lluis F, Ballestar E, Suelves M, Esteller M, Munoz-Canoves P (2005) E47 phosphorylation by p38 MAPK promotes MyoD/E47 association and muscle-specific gene transcription. EMBO J 24:974–984
Lu M, Krauss RS (2010) N-cadherin ligation, but not Sonic hedgehog binding, initiates Cdo-dependent p38α/β MAPK signaling in skeletal myoblasts. Proc Natl Acad Sci U S A 107:4212–4217
Mancini A, Sirabella D, Zhang W, Yamazaki H, Shirao T, Krauss RS (2011) Regulation of myotube formation by the actin-binding factor drebrin. Skelet Muscle 1:36
Mercer JC, Qi Q, Mottram LF, Law M, Bruce D, Iyer A, Morales JL, Yamazaki H, Shirao T, Peterson BR et al (2010) Chemico-genetic identification of drebrin as a regulator of calcium responses. Int J Biochem Cell Biol 42:337–345
Mizui T, Kojima N, Yamazaki H, Katayama M, Hanamura K, Shirao T (2009) Drebrin E is involved in the regulation of axonal growth through actin-myosin interactions. J Neurochem 109:611–622
Moore CA, Parkin CA, Bidet Y, Ingham PW (2007) A role for the Myoblast city homologues Dock1 and Dock5 and the adaptor proteins Crk and Crk-like in zebrafish myoblast fusion. Development 134:3145–3153
Nowak SJ, Nahirney PC, Hadjantonakis AK, Baylies MK (2009) Nap1-mediated actin remodeling is essential for mammalian myoblast fusion. J Cell Sci 122:3282–3293
O’Connor RS, Steeds CM, Wiseman RW, Pavlath GK (2008) Phosphocreatine as an energy source for actin cytoskeletal rearrangements during myoblast fusion. J Physiol 586:2841–2853
Onel SF, Renkawitz-Pohl R (2009) FuRMAS: triggering myoblast fusion in Drosophila. Dev Dyn 238:1513–1525
Pajcini KV, Pomerantz JH, Alkan O, Doyonnas R, Blau HM (2008) Myoblasts and macrophages share molecular components that contribute to cell-cell fusion. J Cell Biol 180:1005–1019
Pallafacchina G, François S, Regnault B, Czarny B, Dive V, Cumano A, Montarras D, Buckingham M (2010) An adult tissue-specific stem cell in its niche: a gene profiling analysis of in vivo quiescent and activated muscle satellite cells. Stem Cell Res 4(2):77–91
Perdiguero E, Ruiz-Bonilla V, Gresh L, Hui L, Ballestar E, Sousa-Victor P, Baeza-Raja B, Jardà M, Bosch-Comas A, Esteller M et al (2007) Genetic analysis of p38 MAP kinases in myogenesis: fundamental role of p38α in abrogating myoblast proliferation. EMBO J 26:1245–1256
Pérez-MartÃnez M, Gordón-Alonso M, Cabrero JR, Barrero-Villar M, Rey M, Mittelbrunn M, Lamana A, Morlino G, Calabia C, Yamazaki H et al (2010) F-actin- binding protein drebrin regulates CXCR4 recruitment to the immune synapse. J Cell Sci 123:1160–1170
Pownall ME, Gustafsson MK, Emerson CP Jr (2002) Myogenic regulatory factors and the specification of muscle progenitors in vertebrate embryos. Annu Rev Cell Dev Biol 18:747–783
Quach NL, Rando TA (2006) Focal adhesion kinase is essential for costamerogenesis in cultured skeletal muscle cells. Dev Biol 293:38–52
Quach NL, Biressi S, Reichardt LF, Keller C, Rando TA (2009) Focal Adhesion Kinase Signaling Regulates the Expression of Caveolin 3 and β1 Integrin, Genes Essential for Normal Myoblast Fusion. Mol Biol Cell 20:3422–3435
Rampalli S, Li L, Mak E, Ge K, Brand M, Tapscott SJ, Dilworth FJ (2007) p38 MAPK signaling regulates recruitment of Ash2L-containing methyltransferase complexes to specific genes during differentiation. Nat Struct Mol Biol 14:1150–1156
Relaix F, Rocancourt D, Mansouri A, Buckingham M (2005) A Pax3/Pax7-dependent population of skeletal muscle progenitor cells. Nature 435:948–953
Richardson BE, Nowak SJ, Baylies MK (2008) Myoblast fusion in fly and vertebrates: new genes, new processes and new perspectives. Traffic 9:1050–1059
Rudnicki MA, Le Grand F, McKinnell I, Kuang S (2008) The Molecular Regulation of Muscle Stem Cell Function. Cold Spring Harb Symp Quant Biol 73:323–331
Schulz RA, Yutzey KE (2004) Calcineurin signaling and NFAT activation in cardiovascular and skeletal muscle development. Dev Biol 266:1–16
Shiraishi-Yamaguchi Y, Sato Y, Sakai R, Mizutani A, Knöpfel T, Mori N, Mikoshiba K, Furuichi T (2009) Interaction of Cupidin/Homer2 with two actin cytoskeletal regulators, Cdc42 small GTPase and Drebrin, in dendritic spines. BMC Neurosci 10:25
Simone C, Forcales SV, Hill DA, Imbalzano AN, Latella L, Puri PL (2004) p38 pathway targets SWI-SNF chromatin-remodeling complex to muscle-specific loci. Nat Genet 36:738–743
Sohn RL, Huang P, Kawahara G, Mitchell M, Guyon J, Kalluri R, Kunkel LM, Gussoni E (2009) A role for nephrin, a renal protein, in vertebrate skeletal muscle cell fusion. Proc Natl Acad Sci U S A 106:9274–9279
Sorci G, Riuzzi F, Arcuri C, Giambanco I, Donato R (2004) Amphoterin stimulates myogenesis and counteracts the antimyogenic factors basic fibroblast growth factor and S100B via RAGE binding. Mol Cell Biol 24:4880–4894
Srinivas BP, Woo J, Leong WY, Roy S (2007) A conserved molecular pathway mediates myoblast fusion in insects and vertebrates. Nat Genet 39:781–786
Stiber JA, Tabatabaei N, Hawkins AF, Hawke T, Worley PF, Williams RS, Rosenberg P (2005) Homer modulates NFAT-dependent signaling during muscle differentiation. Dev Biol 287:213–224
Straube A, Merdes A (2007) EB3 regulates microtubule dynamics at the cell cortex and is required for myoblast elongation and fusion. Curr Biol 17:1318–1325
Tajbakhsh S, Buckingham M (2000) The birth of muscle progenitor cells in the mouse: spatiotemporal considerations. Curr Top Dev Biol 48:225–268
Takaesu G, Kang JS, Bae GU, Yi MJ, Lee CM, Reddy EP, Krauss RS (2006) Activation of p38α/β MAPK in myogenesis via binding of the scaffold protein JLP to the cell surface protein Cdo. J Cell Biol 175:383–388
Tamir Y, Bengal E (2000) Phosphoinositide 3-kinase induces the transcriptional activity of MEF2 proteins during muscle differentiation. J Biol Chem 275:34424–34432
Tapscott SJ (2005) The circuitry of a master switch: myod and the regulation of skeletal muscle gene transcription. Development 132:2685–2695
Trevillyan J, Chiou XG, Chen YW, Ballaron SJ, Sheets MP, Smith ML, Wiedeman PE, Warrior U, Wilkins J, Gubbins EJ et al (2001) Potent inhibition of NFAT activation and T cell cytokine production by novel low molecular weight pyrazole compounds. J Biol Chem 276:48118–48126
Vasyutina E, Martarelli B, Brakebusch C, Wende H, Birchmeier C (2009) The small G-proteins Rac1 and Cdc42 are essential for myoblast fusion in the mouse. Proc Natl Acad Sci U S A 106:8935–8940
Wu Z, Woodring PJ, Bhakta KS, Tamura K, Wen F, Feramisco JR, Karin M, Wang JY, Puri PL (2000) p38 and extracellular signal-regulated kinases regulate the myogenic program at multiple steps. Mol Cell Biol 20:3951–3964
Zetser A, Gredinger E, Bengal E (1999) p38 mitogen-activated protein kinase pathway promotes skeletal muscle differentiation. Participation of the Mef2c transcription factor. J Biol Chem 274:5193–5200
Zhang T, Zaal KJ, Sheridan J, Mehta A, Gundersen GG, Ralston E (2009) Microtubule plus-end binding protein EB1 is necessary for muscle cell differentiation, elongation and fusion. J Cell Sci 122:1401–1409
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2017 Springer Japan KK
About this chapter
Cite this chapter
Krauss, R.S. (2017). Regulation of Skeletal Myoblast Differentiation by Drebrin. In: Shirao, T., Sekino, Y. (eds) Drebrin. Advances in Experimental Medicine and Biology, vol 1006. Springer, Tokyo. https://doi.org/10.1007/978-4-431-56550-5_22
Download citation
DOI: https://doi.org/10.1007/978-4-431-56550-5_22
Published:
Publisher Name: Springer, Tokyo
Print ISBN: 978-4-431-56548-2
Online ISBN: 978-4-431-56550-5
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)