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© The Rockefeller University Press, 0021-9525/1999//893 $5.00
The Journal of Cell Biology, Volume 146, Number 4, , 1999 893-904

Original Article

Role of Transmembrane 4 Superfamily (Tm4sf) Proteins Cd9 and Cd81 in Muscle Cell Fusion and Myotube Maintenance



Isao Tachibanaa and Martin E. Hemlera

a Dana-Farber Cancer Institute, and Harvard Medical School, Boston, Massachusetts 02115
Dana-Farber Cancer Institute, Rm. D-1430, 44 Binney St., Boston, MA 02115.(617) 632-2662(617) 632-3410

martin_hemler{at}dfci.harvard.edu

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–β1 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.

Key Words: TM4SF proteins • CD9 • CD81 • myoblast • myotube

© 1999 The Rockefeller University Press

1.used in this paper: MFI, mean fluorescence intensity; MHC, myosin heavy chain; N-CAM, neural cell adhesion molecule; PKC, protein kinase C; TM4SF, transmembrane 4 superfamily; TUNEL, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling

I. Tachibana's present address is Department of Molecular Medicine, Osaka University Medical School, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.


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