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Molecular Mechanisms of Myoblast Fusion Across Species

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Cell Fusion in Health and Disease

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 713))

Abstract

Skeletal muscle development, growth and regeneration depend on the ability of progenitor myoblasts to fuse to one another in a series of ordered steps. Whereas the cellular steps leading to the formation of a multinucleated myofiber are conserved in several model organisms, the molecular regulatory factors may vary. Understanding the common and divergent mechanisms regulating myoblast fusion in Drosophila melanogaster (fruit fly), Danio rerio (zebrafish) and Mus musculus (mouse) provides a better insight into the process of myoblast fusion than any of these models could provide alone. Deciphering the mechanisms of myoblast fusion from simpler to more complex organisms is of fundamental interest to skeletal muscle biology and may provide therapeutic avenues for various diseases that affect muscle.

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References

  1. Bate M (1990) The embryonic development of larval muscles in Drosophila. Development 110:791–804

    PubMed  CAS  Google Scholar 

  2. Baylies MK, Bate M, Ruiz Gomez M (1998) Myogenesis: a view from Drosophila. Cell 93:921–927

    Article  PubMed  CAS  Google Scholar 

  3. Beckett K, Baylies MK (2007) 3D analysis of founder cell and fusion competent myoblast arrangements outlines a new model of myoblast fusion. Dev Biol 309:113–125

    Article  PubMed  CAS  Google Scholar 

  4. Onel SF, Renkawitz-Pohl R (2009) FuRMAS: triggering myoblast fusion in Drosophila. Dev Dyn 238:1513–1525

    Article  PubMed  CAS  Google Scholar 

  5. Richardson B, Beckett K, Baylies M (2008) Visualizing new dimensions in Drosophila myoblast fusion. Bioessays 30:423–431

    Article  PubMed  Google Scholar 

  6. Roy S, VijayRaghavan K (1999) Muscle pattern diversification in Drosophila: the story of imaginal myogenesis. BioEssays 21:486–498

    Article  PubMed  CAS  Google Scholar 

  7. Richardson BE, Beckett K, Nowak SJ et al (2007) SCAR/WAVE and Arp2/3 are crucial for cytoskeletal remodeling at the site of myoblast fusion. Development 134:4357–4367

    Article  PubMed  CAS  Google Scholar 

  8. Strunkelnberg M, Bonengel B, Moda LM et al (2001) rst and its paralogue kirre act redundantly during embryonic muscle development in Drosophila. Development 128:4229–4239

    PubMed  CAS  Google Scholar 

  9. Ruiz-Gomez M, Coutts N, Price A et al (2000) Drosophila dumbfounded: a myoblast attractant essential for fusion. Cell 102:189–198

    Article  PubMed  CAS  Google Scholar 

  10. Bour BA, Chakravarti M, West JM et al (2000) Drosophila SNS, a member of the immunoglobulin superfamily that is essential for myoblast fusion. Genes Dev 14:1498–1511

    PubMed  CAS  Google Scholar 

  11. Artero RD, Castanon I, Baylies MK (2001) The immunoglobulin-like protein Hibris functions as a dose-dependent regulator of myoblast fusion and is differentially controlled by Ras and Notch signaling. Development 128:4251–4264

    PubMed  CAS  Google Scholar 

  12. Dworak HA, Charles MA, Pellerano LB et al (2001) Characterization of Drosophila hibris, a gene related to human nephrin. Development 128:4265–4276

    PubMed  CAS  Google Scholar 

  13. Shelton C, Kocherlakota KS, Zhuang S et al (2009) The immunoglobulin superfamily member Hbs functions redundantly with Sns in interactions between founder and fusion-competent myoblasts. Development 136:1159–1168

    Article  PubMed  CAS  Google Scholar 

  14. Galletta BJ, Chakravarti M, Banerjee R et al (2004) SNS: Adhesive properties, localization requirements and ectodomain dependence in S2 cells and embryonic myoblasts. Mech Dev 121:1455–1468

    Article  PubMed  CAS  Google Scholar 

  15. Rogers SL, Rogers GC (2008) Culture of Drosophila S2 cells and their use for RNAi-mediated loss-of-function studies and immunofluorescence microscopy. Nat Protoc 3:606–611

    Article  PubMed  CAS  Google Scholar 

  16. Luo L, Liao YJ, Jan LY et al (1994) Distinct morphogenetic functions of similar small GTPases: Drosophila Drac1 is involved in axonal outgrowth and myoblast fusion. Genes Dev 8:1787–1802

    Article  PubMed  CAS  Google Scholar 

  17. Doberstein SK, Fetter RD, Mehta AY et al (1997) Genetic analysis of myoblast fusion: blown fuse is required for progression beyond the prefusion complex. J Cell Biol 136:1249–1261

    Article  PubMed  CAS  Google Scholar 

  18. Chen EH, Olson EN (2001) Antisocial, an intracellular adaptor protein, is required for myoblast fusion in Drosophila. Dev Cell 1:705–715

    Article  PubMed  CAS  Google Scholar 

  19. Rau A, Buttgereit D, Holz A et al (2001) rolling pebbles (rols) is required in Drosophila muscle precursors for recruitment of myoblasts for fusion. Development 128:5061–5073

    PubMed  CAS  Google Scholar 

  20. Menon SD, Chia W (2001) Drosophila rolling pebbles: a multidomain protein required for myoblast fusion that recruits D-Titin in response to the myoblast attractant Dumbfounded. Dev Cell 1:691–703

    Article  PubMed  CAS  Google Scholar 

  21. Chen EH, Pryce BA, Tzeng JA et al (2003) Control of myoblast fusion by a guanine nucleotide exchange factor, loner, and its effector ARF6. Cell 114:751–762

    Article  PubMed  CAS  Google Scholar 

  22. Menon SD, Osman Z, Chenchill K et al (2005) A positive feedback loop between Dumbfounded and Rolling pebbles leads to myotube enlargement in Drosophila. J Cell Biol 169:909–920

    Article  PubMed  CAS  Google Scholar 

  23. Rushton E, Drysdale R, Abmayr SM et al (1995) Mutations in a novel gene, myoblast city, provide evidence in support of the founder cell hypothesis for Drosophila muscle development. Development 121:1979–1988

    PubMed  CAS  Google Scholar 

  24. Erickson MR, Galletta BJ, Abmayr SM (1997) Drosophila myoblast city encodes a conserved protein that is essential for myoblast fusion, dorsal closure, and cytoskeletal organization. J Cell Biol 138:589–603

    Article  PubMed  CAS  Google Scholar 

  25. Ishimaru S, Ueda R, Hinohara Y et al (2004) PVR plays a critical role via JNK activation in thorax closure during Drosophila metamorphosis. EMBO J 23:3984–3994

    Article  PubMed  CAS  Google Scholar 

  26. Geisbrecht ER, Haralalka S, Swanson SK et al (2008) Drosophila ELMO/CED-12 interacts with Myoblast city to direct myoblast fusion and ommatidial organization. Dev Biol 314:137–149

    Article  PubMed  CAS  Google Scholar 

  27. Galletta BJ, Niu XP, Erickson MR et al (1999) Identification of a Drosophila homologue to vertebrate Crk by interaction with MBC. Gene 228:243–252

    Article  PubMed  CAS  Google Scholar 

  28. Kim S, Shilagardi K, Zhang S et al (2007) A critical function for the actin cytoskeleton in targeted exocytosis of prefusion vesicles during myoblast fusion. Dev Cell 12:571–586

    Article  PubMed  CAS  Google Scholar 

  29. Balagopalan L, Chen MH, Geisbrecht ER et al (2006) The CDM superfamily protein MBC directs myoblast fusion through a mechanism that requires phosphatidylinositol 3,4,5-triphosphate binding but is independent of direct interaction with DCrk. Mol Cell Biol 26:9442–9455

    Article  PubMed  CAS  Google Scholar 

  30. Berger S, Schafer G, Kesper DA et al (2008) WASP and SCAR have distinct roles in activating the Arp2/3 complex during myoblast fusion. J Cell Sci 121:1303–1313

    Article  PubMed  CAS  Google Scholar 

  31. Massarwa R, Carmon S, Shilo BZ et al (2007) WIP/WASp-based actin-polymerization machinery is essential for myoblast fusion in Drosophila. Dev Cell 12:557–569

    Article  PubMed  CAS  Google Scholar 

  32. Schafer G, Weber S, Holz A et al (2007) The Wiskott-Aldrich syndrome protein (WASP) is essential for myoblast fusion in Drosophila. Dev Biol 304:664–674

    Article  PubMed  CAS  Google Scholar 

  33. Gildor B, Massarwa R, Shilo BZ et al (2009) The SCAR and WASp nucleation-promoting factors act sequentially to mediate Drosophila myoblast fusion. EMBO Rep 10:1043–1050

    Article  PubMed  CAS  Google Scholar 

  34. Bogdan S, Klambt C (2003) Kette regulates actin dynamics and genetically interacts with Wave and Wasp. Development 130:4427–4437

    Article  PubMed  CAS  Google Scholar 

  35. Schroter RH, Lier S, Holz A et al (2004) kette and blown fuse interact genetically during the second fusion step of myogenesis in Drosophila. Development 131:4501–4509

    Article  PubMed  CAS  Google Scholar 

  36. Schroter RH, Buttgereit D, Beck L et al (2006) Blown fuse regulates stretching and outgrowth but not myoblast fusion of the circular visceral muscles in Drosophila. Differentiation 74:608–621

    Article  PubMed  CAS  Google Scholar 

  37. Baxendale S, Davison C, Muxworthy C et al (2004) The B-cell maturation factor Blimp-1 specifies vertebrate slow-twitch muscle fiber identity in response to Hedgehog signaling. Nat Genet 36:88–93

    Article  PubMed  CAS  Google Scholar 

  38. Devoto SH, Melancon E, Eisen JS et al (1996) Identification of separate slow and fast muscle precursor cells in vivo, prior to somite formation. Development 122:3371–3380

    PubMed  CAS  Google Scholar 

  39. Roy S, Wolff C, Ingham PW (2001) The u-boot mutation identifies a Hedgehog-regulated myogenic switch for fiber-type diversification in the zebrafish embryo. Genes Dev 15:1563–1576

    Article  PubMed  CAS  Google Scholar 

  40. Blagden CS, Currie PD, Ingham PW et al (1997) Notochord induction of zebrafish slow muscle mediated by Sonic hedgehog. Genes Dev 11:2163–2175

    Article  PubMed  CAS  Google Scholar 

  41. Du SJ, Devoto SH, Westerfield M et al (1997) Positive and negative regulation of muscle cell identity by members of the hedgehog and TGF-beta gene families. J Cell Biol 139:145–156

    Article  PubMed  CAS  Google Scholar 

  42. Ochi H, Westerfield M (2007) Signaling networks that regulate muscle development: lessons from zebrafish. Dev Growth Differ 49:1–11

    Article  PubMed  CAS  Google Scholar 

  43. Srinivas BP, Woo J, Leong WY et al (2007) A conserved molecular pathway mediates myoblast fusion in insects and vertebrates. Nat Genet 39:781–786

    Article  PubMed  CAS  Google Scholar 

  44. Sohn RL, Huang P, Kawahara G et al (2009) A role for nephrin, a renal protein, in vertebrate skeletal muscle cell fusion. Proc Natl Acad Sci USA 106:9274–9279

    Article  PubMed  CAS  Google Scholar 

  45. Moore CA, Parkin CA, Bidet Y et al (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

    Article  PubMed  CAS  Google Scholar 

  46. Kelly AM, Zacks SI (1969) The histogenesis of rat intercostal muscle. J Cell Biol 42:135–153

    Article  PubMed  CAS  Google Scholar 

  47. Harris AJ, Duxson MJ, Fitzsimons RB et al (1989) Myonuclear birthdates distinguish the origins of primary and secondary myotubes in embryonic mammalian skeletal muscles. Development 107:771–784

    PubMed  CAS  Google Scholar 

  48. Ross JJ, Duxson MJ, Harris AJ (1987) Formation of primary and secondary myotubes in rat lumbrical muscles. Development 100:383–394

    PubMed  CAS  Google Scholar 

  49. Biressi S, Molinaro M, Cossu G (2007) Cellular heterogeneity during vertebrate skeletal muscle development. Dev Biol 308:281–293

    Article  PubMed  CAS  Google Scholar 

  50. Biressi S, Tagliafico E, Lamorte G et al (2007) Intrinsic phenotypic diversity of embryonic and fetal myoblasts is revealed by genome-wide gene expression analysis on purified cells. Dev Biol 304:633–651

    Article  PubMed  CAS  Google Scholar 

  51. Hutcheson DA, Zhao J, Merrell A et al (2009) Embryonic and fetal limb myogenic cells are derived from developmentally distinct progenitors and have different requirements for beta-catenin. Genes Dev 23:997–1013

    Article  PubMed  CAS  Google Scholar 

  52. Charge SB, Rudnicki MA (2004) Cellular and molecular regulation of muscle regeneration. Physiol Rev 84:209–238

    Article  PubMed  CAS  Google Scholar 

  53. Sherwood RI, Christensen JL, Conboy IM et al (2004) Isolation of adult mouse myogenic progenitors: functional heterogeneity of cells within and engrafting skeletal muscle. Cell 119:543–554

    Article  PubMed  CAS  Google Scholar 

  54. Ohtake Y, Tojo H, Seiki M (2006) Multifunctional roles of MT1-MMP in myofiber formation and morphostatic maintenance of skeletal muscle. J Cell Sci 119:3822–3832

    Article  PubMed  CAS  Google Scholar 

  55. Swailes NT, Colegrave M, Knight PJ et al (2006) Non-muscle myosins 2A and 2B drive changes in cell morphology that occur as myoblasts align and fuse. J Cell Sci 119:3561–3570

    Article  PubMed  CAS  Google Scholar 

  56. Nowak SJ, Nahirney PC, Hadjantonakis AK et al (2009) Nap1-mediated actin remodeling is essential for mammalian myoblast fusion. J Cell Sci 122:3282–3293

    Article  PubMed  CAS  Google Scholar 

  57. Yoon S, Molloy MJ, Wu MP et al (2007) C6ORF32 is upregulated during muscle cell differentiation and induces the formation of cellular filopodia. Dev Biol 301:70–81

    Article  PubMed  CAS  Google Scholar 

  58. Mukai A, Hashimoto N (2008) Localized cyclic AMP-dependent protein kinase activity is required for myogenic cell fusion. Exp Cell Res 314:387–397

    Article  PubMed  CAS  Google Scholar 

  59. Mukai A, Kurisaki T, Sato SB et al (2009) Dynamic clustering and dispersion of lipid rafts contribute to fusion competence of myogenic cells. Exp Cell Res 315:3052–3063

    Article  PubMed  CAS  Google Scholar 

  60. Stadler B, Blattler TM, Franco-Obregon A (2010) Time-lapse imaging of in vitro myogenesis using atomic force microscopy. J Microsc 237:63–69

    Article  PubMed  CAS  Google Scholar 

  61. 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

    Article  PubMed  CAS  Google Scholar 

  62. Krauss RS, Cole F, Gaio U et al (2005) Close encounters: regulation of vertebrate skeletal myogenesis by cell-cell contact. J Cell Sci 118:2355–2362

    Article  PubMed  CAS  Google Scholar 

  63. Griffin CA, Kafadar KA, Pavlath GK (2009) MOR23 promotes muscle regeneration and regulates cell adhesion and migration. Dev Cell 17:649–661

    Article  PubMed  CAS  Google Scholar 

  64. Jansen KM, Pavlath GK (2006) Mannose receptor regulates myoblast motility and muscle growth. J Cell Biol 174:403–413

    Article  PubMed  CAS  Google Scholar 

  65. Horsley V, Jansen KM, Mills ST et al (2003) IL-4 acts as a myoblast recruitment factor during mammalian muscle growth. Cell 113:483–494

    Article  PubMed  CAS  Google Scholar 

  66. Lafreniere JF, Mills P, Bouchentouf M et al (2006) Interleukin-4 improves the migration of human myogenic precursor cells in vitro and in vivo. Exp Cell Res 312:1127–1141

    Article  PubMed  CAS  Google Scholar 

  67. Bondesen BA, Jones KA, Glasgow WC et al (2007) Inhibition of myoblast migration by prostacyclin is associated with enhanced cell fusion. FASEB J 21:3338–3345

    Article  PubMed  CAS  Google Scholar 

  68. Knudsen KA (1985) The calcium-dependent myoblast adhesion that precedes cell fusion is mediated by glycoproteins. J Cell Biol 101:891–897

    Article  PubMed  CAS  Google Scholar 

  69. Charrasse S, Comunale F, Fortier M et al (2007) M-cadherin activates Rac1 GTPase through the Rho-GEF trio during myoblast fusion. Mol Biol Cell 18:1734–1743

    Article  PubMed  CAS  Google Scholar 

  70. Li H, Lemay S, Aoudjit L et al (2004) SRC-family kinase Fyn phosphorylates the cytoplasmic domain of nephrin and modulates its interaction with podocin. J Am Soc Nephrol 15:3006–3015

    Article  PubMed  Google Scholar 

  71. Lipton BH, Konigsberg IR (1972) A fine-structural analysis of the fusion of myogenic cells. J Cell Biol 53:348–364

    Article  PubMed  CAS  Google Scholar 

  72. Rash JE, Fambrough D (1973) Ultrastructural and electrophysiological correlates of cell coupling and cytoplasmic fusion during myogenesis in vitro. Dev Biol 30:166–186

    Article  PubMed  CAS  Google Scholar 

  73. Wakelam MJ (1985) The fusion of myoblasts. Biochem J 228:1–12

    PubMed  CAS  Google Scholar 

  74. Kalderon N, Gilula NB (1979) Membrane events involved in myoblast fusion. J Cell Biol 81:411–425

    Article  PubMed  CAS  Google Scholar 

  75. Robertson TA, Grounds MD, Mitchell CA et al (1990) Fusion between myogenic cells in vivo: an ultrastructural study in regenerating murine skeletal muscle. J Struct Biol 105:170–182

    Article  PubMed  CAS  Google Scholar 

  76. Fulton AB, Prives J, Farmer SR et al (1981) Developmental reorganization of the skeletal framework and its surface lamina in fusing muscle cells. J Cell Biol 91:103–112

    Article  PubMed  CAS  Google Scholar 

  77. Duan R, Gallagher PJ (2009) Dependence of myoblast fusion on a cortical actin wall and nonmuscle myosin IIA. Dev Biol 325:374–385

    Article  PubMed  CAS  Google Scholar 

  78. Swailes NT, Knight PJ, Peckham M (2004) Actin filament organization in aligned prefusion myoblasts. J Anat 205:381–391

    Article  PubMed  Google Scholar 

  79. O’Connor RS, Steeds CM, Wiseman RW et al (2008) Phosphocreatine as an energy source for actin cytoskeletal rearrangements during myoblast fusion. J Physiol 586:2841–2853

    Article  PubMed  CAS  Google Scholar 

  80. Kurisu S, Takenawa T (2009) The WASP and WAVE family proteins. Genome Biol 10:226

    Article  PubMed  CAS  Google Scholar 

  81. Hynes RO (2002) Integrins: bidirectional, allosteric signaling machines. Cell 110:673–687

    Article  PubMed  CAS  Google Scholar 

  82. Gullberg D (2003) Cell biology: the molecules that make muscle. Nature 424:138–140

    Article  PubMed  CAS  Google Scholar 

  83. Schwander M, Leu M, Stumm M et al (2003) Beta1 integrins regulate myoblast fusion and sarcomere assembly. Dev Cell 4:673–685

    Article  PubMed  CAS  Google Scholar 

  84. Quach NL, Biressi S, Reichardt LF et al (2009) Focal adhesion kinase signaling regulates the expression of caveolin 3 and beta1 integrin, genes essential for normal myoblast fusion. Mol Biol Cell 20:3422–3435

    Article  PubMed  CAS  Google Scholar 

  85. Horsley V, Friday BB, Matteson S et al (2001) Regulation of the growth of multinucleated muscle cells by an NFATC2-dependent pathway. J Cell Biol 153:329–338

    Article  PubMed  CAS  Google Scholar 

  86. Muroya S, Takagi H, Tajima S et al (1994) Selective inhibition of a step of myotube formation with wheat germ agglutinin in a murine myoblast cell line, C2C12. Cell Struct Funct 19:241–252

    Article  PubMed  CAS  Google Scholar 

  87. Maecker HT, Todd SC, Levy S (1997) The tetraspanin superfamily: molecular facilitators. FASEB J 11:428–442

    PubMed  CAS  Google Scholar 

  88. Tachibana I, Hemler ME (1999) Role of transmembrane 4 superfamily (TM4SF) proteins CD9 and CD81 in muscle cell fusion and myotube maintenance. J Cell Biol 146:893–904

    Article  PubMed  CAS  Google Scholar 

  89. Gorza L, Vitadello M (2000) Reduced amount of the glucose-regulated protein GRP94 in skeletal myoblasts results in loss of fusion competence. FASEB J 14:461–475

    PubMed  CAS  Google Scholar 

  90. Wanderling S, Simen BB, Ostrovsky O et al (2007) GRP94 is essential for mesoderm induction and muscle development because it regulates insulin-like growth factor secretion. Mol Biol Cell 18:3764–3775

    Article  PubMed  CAS  Google Scholar 

  91. Bois PR, Grosveld GC (2003) FKHR (FOXO1a) is required for myotube fusion of primary mouse myoblasts. EMBO J 22:1147–1157

    Article  PubMed  CAS  Google Scholar 

  92. Nishiyama T, Kii I, Kudo A (2004) Inactivation of Rho/ROCK signaling is crucial for the nuclear accumulation of FKHR and myoblast fusion. J Biol Chem 279:47311–47319

    Article  PubMed  CAS  Google Scholar 

  93. Bois PR, Brochard VF, Salin-Cantegrel AV et al (2005) FoxO1a-cyclic GMP-dependent kinase I interactions orchestrate myoblast fusion. Mol Cell Biol 25:7645–7656

    Article  PubMed  CAS  Google Scholar 

  94. Shafey D, Cote PD, Kothary R (2005) Hypomorphic Smn knockdown C2C12 myoblasts reveal intrinsic defects in myoblast fusion and myotube morphology. Exp Cell Res 311:49–61

    Article  PubMed  CAS  Google Scholar 

  95. Lee SJ, McPherron AC (2001) Regulation of myostatin activity and muscle growth. Proc Natl Acad Sci USA 98:9306–9311

    Article  PubMed  CAS  Google Scholar 

  96. Lee KH, Baek MY, Moon KY et al (1994) Nitric oxide as a messenger molecule for myoblast fusion. J Biol Chem 269:14371–14374

    PubMed  CAS  Google Scholar 

  97. Pisconti A, Brunelli S, Di Padova M et al (2006) Follistatin induction by nitric oxide through cyclic GMP: a tightly regulated signaling pathway that controls myoblast fusion. J Cell Biol 172:233–244

    Article  PubMed  CAS  Google Scholar 

  98. Long JH, Lira VA, Soltow QA et al (2006) Arginine supplementation induces myoblast fusion via augmentation of nitric oxide production. J Muscle Res Cell Motil 27:577–584

    Article  PubMed  CAS  Google Scholar 

  99. Iezzi S, Di Padova M, Serra C et al (2004) Deacetylase inhibitors increase muscle cell size by promoting myoblast recruitment and fusion through induction of follistatin. Dev Cell 6:673–684

    Article  PubMed  CAS  Google Scholar 

  100. Park IH, Chen J (2005) Mammalian target of rapamycin (mTOR) signaling is required for a late-stage fusion process during skeletal myotube maturation. J Biol Chem 280:32009–32017

    Article  PubMed  CAS  Google Scholar 

  101. Ge Y, Wu AL, Warnes C et al (2009) mTOR regulates skeletal muscle regeneration in vivo through kinase-dependent and kinase-independent mechanisms. Am J Physiol Cell Physiol 297:C1434–1444

    Article  CAS  Google Scholar 

  102. Sun Y, Ge Y, Drnevich J et al (2010) Mammalian target of rapamycin regulates miRNA-1 and follistatin in skeletal myogenesis. J Cell Biol 189:1157–1169

    Article  PubMed  CAS  Google Scholar 

  103. Pavlath GK, Horsley V (2003) Cell fusion in skeletal muscle–central role of NFATC2 in regulating muscle cell size. Cell Cycle 2:420–423

    Article  PubMed  CAS  Google Scholar 

  104. Horsley V, Pavlath GK (2003) Prostaglandin F2(alpha) stimulates growth of skeletal muscle cells via an NFATC2-dependent pathway. J Cell Biol 161:111–118

    Article  PubMed  CAS  Google Scholar 

  105. Sotiropoulos A, Ohanna M, Kedzia C et al (2006) Growth hormone promotes skeletal muscle cell fusion independent of insulin-like growth factor 1 up-regulation. Proc Natl Acad Sci USA 103:7315–7320

    Article  PubMed  CAS  Google Scholar 

  106. Jansen KM, Pavlath GK (2008) Prostaglandin F2alpha promotes muscle cell survival and growth through upregulation of the inhibitor of apoptosis protein BRUCE. Cell Death Differ 15:1619–1628

    Article  PubMed  CAS  Google Scholar 

  107. Fornaro M, Burch PM, Yang W et al (2006) SHP-2 activates signaling of the nuclear factor of activated T cells to promote skeletal muscle growth. J Cell Biol 175:87–97

    Article  PubMed  CAS  Google Scholar 

  108. Zeschnigk M, Kozian D, Kuch C et al (1995) Involvement of M-cadherin in terminal differentiation of skeletal muscle cells. J Cell Sci 108 (Pt 9):2973–2981

    PubMed  CAS  Google Scholar 

  109. Charrasse S, Comunale F, Grumbach Y et al (2006) RhoA GTPase regulates M-cadherin activity and myoblast fusion. Mol Biol Cell 17:749–759

    Article  PubMed  CAS  Google Scholar 

  110. Hollnagel A, Grund C, Franke WW et al (2002) The cell adhesion molecule M-cadherin is not essential for muscle development and regeneration. Mol Cell Biol 22:4760–4770

    Article  PubMed  CAS  Google Scholar 

  111. Bach AS, Enjalbert S, Comunale F et al (2010) ADP-ribosylation factor 6 regulates mammalian myoblast fusion through phospholipase D1 and phosphatidylinositol 4,5-bisphosphate signaling pathways. Mol Biol Cell 21:2412–2424

    Article  PubMed  CAS  Google Scholar 

  112. Donaldson JG (2008) Arfs and membrane lipids: sensing, generating and responding to membrane curvature. Biochem J 414:e1–2

    Article  CAS  Google Scholar 

  113. Kramerova I, Kudryashova E, Tidball JG et al (2004) Null mutation of calpain 3 (p94) in mice causes abnormal sarcomere formation in vivo and in vitro. Hum Mol Genet 13:1373–1388

    Article  PubMed  CAS  Google Scholar 

  114. Kramerova I, Kudryashova E, Wu B et al (2006) Regulation of M-cadherin -{beta}-catenin complex by calpain 3 during terminal stages of myogenic differentiation. Mol Cell Biol 26:8437–8447

    Article  PubMed  CAS  Google Scholar 

  115. Fortier M, Comunale F, Kucharczak J et al (2008) RhoE controls myoblast alignment prior fusion through RhoA and ROCK. Cell Death Differ 15:1221–1231

    Article  PubMed  CAS  Google Scholar 

  116. Volonte D, Peoples AJ, Galbiati F (2003) Modulation of myoblast fusion by caveolin-3 in dystrophic skeletal muscle cells: implications for Duchenne muscular dystrophy and limb-girdle muscular dystrophy-1C. Mol Biol Cell 14:4075–4088

    Article  PubMed  CAS  Google Scholar 

  117. Dupressoir A, Marceau G, Vernochet C et al (2005) Syncytin-A and syncytin-B, two fusogenic placenta-specific murine envelope genes of retroviral origin conserved in Muridae. Proc Natl Acad Sci USA 102:725–730

    Article  PubMed  CAS  Google Scholar 

  118. Dupressoir A, Vernochet C, Bawa O et al (2009) Syncytin-A knockout mice demonstrate the critical role in placentation of a fusogenic, endogenous retrovirus-derived, envelope gene. Proc Natl Acad Sci USA 106:12127–12132

    Article  PubMed  CAS  Google Scholar 

  119. Laurin M, Fradet N, Blangy A et al (2008) The atypical Rac activator Dock180 (Dock1) regulates myoblast fusion in vivo. Proc Natl Acad Sci USA 105:15446–15451

    Article  PubMed  CAS  Google Scholar 

  120. Pajcini KV, Pomerantz JH, Alkan O et al (2008) Myoblasts and macrophages share molecular components that contribute to cell-cell fusion. J Cell Biol 180:1005–1019

    Article  PubMed  CAS  Google Scholar 

  121. Vasyutina E, Martarelli B, Brakebusch C et al (2009) The small G-proteins Rac1 and Cdc42 are essential for myoblast fusion in the mouse. Proc Natl Acad Sci USA 106:8935–8940

    Article  PubMed  CAS  Google Scholar 

  122. 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

    Article  PubMed  CAS  Google Scholar 

  123. Dowling JJ, Vreede AP, Kim S et al (2008) Kindlin-2 is required for myocyte elongation and is essential for myogenesis. BMC Cell Biol 9:36

    Article  PubMed  CAS  Google Scholar 

  124. Bae GU, Gaio U, Yang YJ et al (2008) Regulation of myoblast motility and fusion by the CXCR4-associated sialomucin, CD164. J Biol Chem 283:8301–8309

    Article  PubMed  CAS  Google Scholar 

  125. Suzuki M, Angata K, Nakayama J et al (2003) Polysialic acid and mucin type o-glycans on the neural cell adhesion molecule differentially regulate myoblast fusion. J Biol Chem 278:49459–49468

    Article  PubMed  CAS  Google Scholar 

  126. Rosen GD, Sanes JR, LaChance R et al (1992) Roles for the integrin VLA-4 and its counter receptor VCAM-1 in myogenesis. Cell 69:1107–1119

    Article  PubMed  CAS  Google Scholar 

  127. Dalkilic I, Schienda J, Thompson TG et al (2006) Loss of FilaminC (FLNc) results in severe defects in myogenesis and myotube structure. Mol Cell Biol 26:6522–6534

    Article  PubMed  CAS  Google Scholar 

  128. Conti FJ, Monkley SJ, Wood MR et al (2009) Talin 1 and 2 are required for myoblast fusion, sarcomere assembly and the maintenance of myotendinous junctions. Development 136:3597–3606

    Article  PubMed  CAS  Google Scholar 

  129. Doherty KR, Demonbreun AR, Wallace GQ et al (2008) The endocytic recycling protein EHD2 interacts with myoferlin to regulate myoblast fusion. J Biol Chem 283:20252–20260

    Article  PubMed  CAS  Google Scholar 

  130. Doherty KR, Cave A, Davis DB et al (2005) Normal myoblast fusion requires myoferlin. Development 132:5565–5575

    Article  PubMed  CAS  Google Scholar 

  131. Kamei Y, Miura S, Suzuki M et al (2004) Skeletal muscle FOXO1 (FKHR) transgenic mice have less skeletal muscle mass, down-regulated Type I (slow twitch/red muscle) fiber genes, and impaired glycemic control. J Biol Chem 279:41114–41123

    Article  PubMed  CAS  Google Scholar 

  132. Ostrovsky O, Eletto D, Makarewich C et al (2009) Glucose regulated protein 94 is required for muscle differentiation through its control of the autocrine production of insulin-like growth factors. Biochim Biophys Acta 1803:333–341

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmacology, Emory University, Atlanta, GA, 30322, USA

    Adriana Simionescu & Grace K. Pavlath

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  1. Adriana Simionescu
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  2. Grace K. Pavlath
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Correspondence to Grace K. Pavlath .

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  1. University of Witten/Herdecke Institute of Immunology, Stockumer Str. 10, 58448, Witten, Germany

    Thomas Dittmar  & Kurt S. Zänker  & 

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Simionescu, A., Pavlath, G.K. (2011). Molecular Mechanisms of Myoblast Fusion Across Species. In: Dittmar, T., Zänker, K.S. (eds) Cell Fusion in Health and Disease. Advances in Experimental Medicine and Biology, vol 713. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-0763-4_8

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