Beta1 integrins regulate myoblast fusion and sarcomere assembly.
The mechanisms that regulate the formation of multinucleated muscle fibers from mononucleated myoblasts are not well understood. We show here that extracellular matrix (ECM) receptors of the beta1 integrin family regulate myoblast fusion. beta1-deficient myoblasts adhere to each other, but plasma membrane breakdown is defective. The integrin-associated tetraspanin CD9 that regulates cell fusion is no longer expressed at the cell surface of beta1-deficient myoblasts, suggesting that beta1 integrins regulate the formation of a protein complex important for fusion. Subsequent to fusion, beta1 integrins are required for the assembly of sarcomeres. Other ECM receptors such as the dystrophin glycoprotein complex are still expressed but cannot compensate for the loss of beta1 integrins, providing evidence that different ECM receptors have nonredundant functions in skeletal muscle fibers.
Friedrich Miescher Institute, Maulbeerstr 66, 4058 Basel, Switzerland.
Martin
M
Schwander
Marco
M
Leu
Michael
M
Stumm
Olivier M
OM
Dorchies
Urs T
UT
Ruegg
Johannes
J
Schittny
Ulrich
U
Müller
D000818:Animals; D016923:Cell Death; D002455:Cell Division; D002459:Cell Fusion; D002465:Cell Movement; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008854:Microscopy, Electron; D018482:Muscle, Skeletal / Q000166:cytology / Q000196:embryology / Q000648:ultrastructure; D032446:Myoblasts / Q000166:cytology* / Q000378:metabolism* / Q000648:ultrastructure; D012518:Sarcomeres / Q000378:metabolism*
D019012:Integrin beta1