Skip to main content
SpringerLink
Log in
Book cover

Cell Fusions pp 267–275Cite as

The Endogenous Envelope Protein Syncytin Is Involved in Myoblast Fusion

  • Chapter
  • First Online:

Abstract

Development of human skeletal muscle depends upon fusion of myoblast s to form multinucleated muscle fibers . Many factors are important to this process, but, so far, molecules directly mediating fusions have not been identified. In man, the highly conserved endogenous retroviral envelope protein syncytin-1 is the best candidate for a true fusogen. Here, we summarize data showing that syncytin-1 and its receptors ASCT-1 and -2 are expressed in human myoblasts and that syncytin-1 is involved in myoblast fusion. These data suggest a more wide-ranging biological role for this endogenous retroviral envelope gene that hitherto suspected.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Abbreviations

ADAM:

A disintegrin and metalloproteinase domain

ASCT:

Alanine, serine and cysteine-selective transporters

CD:

Cluster of differentiation

EFF-1:

Epithelial fusion failure

ERV:

Endogenous retrovirus

F-actin:

Filamentous actin

GADPH:

Glyceraldehyde 3-phosphate dehydrogenase,

GCM:

Glial cell missing

HERV:

Human endogenous retrovirus

IL:

Interleukin

MFSD2:

Major facilitator superfamily domain containing 2

NCAM:

Neural cell adhesion molecule

NFATc2:

Nuclear factor of activated T cells c2

PCR:

Polymerase chain reaction

RT:

Reverse transcriptase

VCAM:

Vascular cell adhesion molecule

References

  • Antony JM, van Marle G, Opii W et al (2004) Human endogenous retrovirus glycoprotein-mediated induction of redox reactants causes oligodendrocyte death and demyelination. Nat Neurosci 7:1088–1095

    Article  CAS  PubMed  Google Scholar 

  • Bjerregaard B, Holck S, Christensen I J et al (2006) Syncytin is involved in breast cancer-endothelial cell fusions. Cell Mol Life Sci 63:1906–19

    Article  Google Scholar 

  • Blond J, Lavillette D, Cheynet V et al (2000) An envelope glycoprotein of the human endogenous retrovirus HERV-W is expressed in the human placenta and fuses cells expressing the type D mammalian retrovirus receptor. J Virol 74:3321–3329

    Article  CAS  PubMed  Google Scholar 

  • Chang C, Chen PT, Chang GD et al (2004) Functional characterization of the placental fusogenic membrane protein syncytin. Biol Reprod 71:1956–1962

    Article  CAS  PubMed  Google Scholar 

  • Chang CW, Chuang HC, Yu C et al (2005) Stimulation of GCMa transcriptional activity by cyclic AMP/protein kinase A signaling is attributed to CBP-mediated acetylation of GCMa. Mol Cell Biol 25:8401–8414

    Article  CAS  PubMed  Google Scholar 

  • Charlton CA, Mohler WA, Blau HM (2000) Neural cell adhesion molecule (NCAM) and myoblast fusion. Dev Biol 221:112–119

    Article  CAS  PubMed  Google Scholar 

  • 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  CAS  PubMed  Google Scholar 

  • Chen EH, Olson EN (2005) Unveiling the mechanisms of cell–cell fusion. Science 308:369–373

    CAS  Google Scholar 

  • Cheynet V, Ruggieri A, Oriol G et al (2005) Synthesis, assembly and processing of the Env ERVWE1/syncytin human endogenous retroviral envelope. J Virol 79:5585–5593

    Article  CAS  PubMed  Google Scholar 

  • Cheynet V, Oriol G, Mallet F (2006) Identification of the hASCT2-binding domain of the Env ERVWE1/syncytin-1 fusogenic glycoprotein. Retrovirology 3:41

    Article  PubMed  Google Scholar 

  • 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  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • 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  CAS  PubMed  Google Scholar 

  • Esnault C, Priet S, Ribet D et al (2008) A placenta-specific receptor or the fusogenic, endogenous retrovirus-derived, human syncytin-2. Proc Natl Acad Sci USA. 105:17532–17537

    Article  CAS  PubMed  Google Scholar 

  • Frendo JL, Olivier D, Cheynet V et al (2003) Direct involvement of HERV-W Env glycoprotein in human trophoblast cell fusion and differentiation. Mol Cell Biol 23:3566–3574

    Article  CAS  PubMed  Google Scholar 

  • Galbiati F, Volonte D, Engelman JA et al (1999) Targeted down-regulation of caveolin-3 is sufficient to inhibit myotube formation in differentiating C2C12 myoblasts. Transient activation of p38 mitogen-activated protein kinase is required for induction of caveolin-3 expression and subsequent myotube formation. J Biol Chem 274:30315–30321

    Article  CAS  PubMed  Google Scholar 

  • Gong R, Huang L, Shi J et al (2007) Syncytin-A mediates the formation of syncytiotrophoblast involved in mouse placental development. Cell Physiol Biochem 20:517–526

    Article  CAS  PubMed  Google Scholar 

  • Heidmann O, Vernochet C, Dupressoir A et al (2009) Identification of an endogenous retroviral envelope gene with fusogenic activity and placenta-specific expression in the rabbit: a new “syncytin” in a third order of mammals. Retrovirology 6:107

    Article  PubMed  Google Scholar 

  • Horsley V, Pavlath GK (2004) Forming a multinucleated cell: molecules that regulate myoblast fusion. Cell Tissues Organs 176:67–78

    Article  Google Scholar 

  • 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  CAS  PubMed  Google Scholar 

  • Knerr I, Schubert SW, Wich C et al (2005) Stimulation of GCMa and syncytin via cAMP mediated PKA signaling in human trophoblastic cells under normoxic and hypoxic conditions. FEBS Lett 579:3991–3998

    Article  CAS  PubMed  Google Scholar 

  • Kim SJ, Kim S, Shin H et al (2008) Intercellular interaction observed by atomic force microscopy. Ultramicroscopy 108:1148–1151

    Article  CAS  PubMed  Google Scholar 

  • Kontarides MI, Eminaga S, Fornaro M et al (2004) SHP-2 positively regulates myogenesis by coupling to the Rho GTPase signaling pathway. Mol Cell Biol 24:5340–5352

    Article  Google Scholar 

  • Larsen JM, Christensen IJ, Nielsen HJ et al (2009) Syncytin immunoreactivity in colorectal cancer: potential prognostic impact. Cancer Lett 280:44–49

    Article  CAS  PubMed  Google Scholar 

  • Larsson LI, Holck S, Christensen IJ (2007) Prognostic role of syncytin expression in breast cancer. Hum Pathol 38:726–731

    Article  CAS  PubMed  Google Scholar 

  • Lavillette D, Marin M, Ruggieri A et al (2000) The envelope glycoprotein of human endogenous retrovirus type W uses a divergent family of amino acid transporters/cell surface receptors. J Virol 76:6442–6452

    Article  Google Scholar 

  • Mi S, Lee X, Li X et al (2000) Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis. Nature 403:785–789

    Article  CAS  PubMed  Google Scholar 

  • Muroi Y, Sakurai T, Hanashi A et al (2009) CD9 regulates transcription factor GCM1 and ERVWE1 expression through the cAMP/protein kinase A signaling pathway. Reproduction 138:945–951

    Article  CAS  PubMed  Google Scholar 

  • Nowak SJ, Nahirney PC, Hadjantonakis AK et al (2010) Nap1-mediated actin remodeling is essential for mammalian myoblast fusion. J Cell Sci 122:3282–3293

    Article  Google Scholar 

  • Oluwole OSA, Yao Y, Conradi S et al (2007) Elevated levels of transcripts encoding a human retroviral envelope protein (syncytin) in muscles from patients with motor neuron disease. Amyotroph Lateral Scler 8:67–72

    Article  CAS  PubMed  Google Scholar 

  • Oren-Suissa M, Podbilewicz B (2007) Cell fusion during development. Trends Cell Biol 17:537–546

    CAS  PubMed  Google Scholar 

  • Pavlath GK, Horsley V (2003) Cell fusion in skeletal muscle. Central role of NFATC2 in regulating muscle cell size. Cell Cycle 2:420–425

    CAS  PubMed  Google Scholar 

  • Sapir A, Avinoam O, Podbilewicz B et al (2008) Viral and developmental cell fusion mechanisms: conservation and divergence. Dev Cell 14:11–21

    Article  CAS  PubMed  Google Scholar 

  • Schwander M, Leu M, Stumm M et al (2003) Beta-1 integrins regulate myoblast fusion and sarcomere assembly. Dev Cell 4:673–685

    Article  CAS  PubMed  Google Scholar 

  • Städler B, Blättler TM, Franco-Obregón A (2010) Time-lapse imaging of in vitro myogenesis using atomic force microscopy. J Microsc 237:63–69

    Article  PubMed  Google Scholar 

  • Strick R, Ackermann S, Langbein M et al (2007) Proliferation and cell–cell fusion of endometrial carcinoma are induced by the human endogenous retroviral syncytin-1 and regulated by TGF-beta. J Mol Med 85:23–38

    Article  CAS  PubMed  Google Scholar 

  • Sun Y, Ouyang DY, Pang W et al (2010) Expression of syncytin in leukemia and lymphoma cells. Leuk Res. doi:10.1016/j.leukres.2010.03.016

    Google Scholar 

  • 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  CAS  PubMed  Google Scholar 

  • Vargas A, Moreau J, Landry S, LeBellego F, Toufaily C, Rassart E, Lafond J, Barbeau B (2009) Syncytin-2 plays an important role in the fusion of human trophoblast cells. J Mol Biol 392:301–318

    Google Scholar 

  • Vargas A, Moreau J, Le Bellego F, Lafond J, Barbeau B (2008) Induction of trophoblast cell fusion by a protein tyrosine phosphatase inhibitor. Placenta 29:170–174

    Google Scholar 

  • Yagami-Hiromasa T, Sato T, Kurisaki T et al (1995) A metalloproteinase-disintegrin participating in myoblast fusion. Nature 377:652–656

    Article  CAS  PubMed  Google Scholar 

  • Yang JT, Rando TA, Mohler WA et al (1996) Genetic analysis of alpha 4 integrin functions in the development of mouse skeletal muscle. J Cell Biol 135:829–835

    Article  CAS  PubMed  Google Scholar 

  • 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  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Cell Biology, Faculty of Life Sciences, University of Copenhagen, DK-1870, Frederiksberg C, Denmark

    Bolette Bjerregaard & Jan Fredrik Talts

  2. Division of Cell Biology, Anatomy, Cell Biology and Genetics, IBHV, Faculty of Life Sciences, University of Copenhagen, 1809, Frederiksberg C, Denmark

    Lars-Inge Larsson

Authors
  1. Bolette Bjerregaard
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jan Fredrik Talts
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lars-Inge Larsson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bolette Bjerregaard .

Editor information

Editors and Affiliations

  1. Faculty of Life Sciences, Division of Cell Biology, University of Copenhagen, Gronnegaardsvej 7, Frederiksberg C, 1870, Denmark

    Lars-Inge Larsson

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media B.V.

About this chapter

Cite this chapter

Bjerregaard, B., Talts, J.F., Larsson, LI. (2011). The Endogenous Envelope Protein Syncytin Is Involved in Myoblast Fusion. In: Larsson, LI. (eds) Cell Fusions. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-9772-9_13

Download citation

Publish with us

Policies and ethics

Search

Navigation