Role of transmembrane 4 superfamily (TM4SF) proteins CD9 and CD81 in muscle cell fusion and myotube maintenance.
The role of transmembrane 4 superfamily (TM4SF) proteins during muscle cell fusion has not been investigated previously. Here we show that the appearance of TM4SF protein, CD9, and the formation of CD9-beta1 integrin complexes were both regulated in coordination with murine C2C12 myoblast cell differentiation. Also, anti-CD9 and anti-CD81 monoclonal antibodies substantially inhibited and delayed conversion of C2C12 cells to elongated myotubes, without affecting muscle-specific protein expression. Studies of the human myoblast-derived RD sarcoma cell line further demonstrated that TM4SF proteins have a role during muscle cell fusion. Ectopic expression of CD9 caused a four- to eightfold increase in RD cell syncytia formation, whereas anti-CD9 and anti-CD81 antibodies markedly delayed RD syncytia formation. Finally, anti-CD9 and anti-CD81 monoclonal antibodies triggered apoptotic degeneration of C2C12 cell myotubes after they were formed. In summary, TM4SF proteins such as CD9 and CD81 appear to promote muscle cell fusion and support myotube maintenance.
Tachibana
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Dana-Farber Cancer Institute, and Harvard Medical School, Boston, Massachusetts 02115, USA.
Hemler
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D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation; D002459:Cell Fusion / Q000187:drug effects; D002460:Cell Line; D053938:DNA Fragmentation / Q000187:drug effects; D003893:Desmin / Q000378:metabolism; D005786:Gene Expression Regulation; D015726:Giant Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006649:Histocompatibility Antigens / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1 / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D011233:Precipitin Tests; D060225:Tetraspanin 28; D060245:Tetraspanin 29; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C554798:CD81 protein, human; C554869:CD9 protein, human; C554799:Cd81 protein, mouse; C554870:Cd9 protein, mouse; D003893:Desmin; D006649:Histocompatibility Antigens; D019012:Integrin beta1; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D060225:Tetraspanin 28; D060245:Tetraspanin 29