Laminins promote the locomotion of skeletal myoblasts via the alpha 7 integrin receptor.
The alpha 7 beta 1 integrin is specifically expressed by skeletal and cardiac muscles, and its expression and alternative mRNA splicing at the cytoplasmic domain are developmentally regulated. We analyzed the role of alpha 7 integrin in mediating myoblast adhesion and motility on different laminin isoforms. Mouse C2C12 and MM14 myoblast cell lines were found by flow cytometry and immunoprecipitation to express high levels of the alpha 7 integrin. Overall expression of alpha 7 increased as the C2C12 myoblasts differentiated; myoblasts expressed only the alpha 7B cytoplasmic variant whereas in differentiating myotubes alpha 7A increased markedly. Function-perturbing monoclonal antibodies generated to alpha 7 integrin efficiently blocked both adhesion and migration of MM14 and C2C12 mouse myoblasts on laminin 1. Other studies with MM14 myoblasts showed that alpha 7 is also a receptor for laminin 2/4 (human placental merosins) but not for epithelial-cell-specific laminin 5. Blocking antibody to alpha 7 only partially inhibited adhesion to laminin 2/4 but almost completely blocked motility on this substrate. Finally, to assess the potential role of the alpha 7 cytoplasmic domain, CHO cells were stably transfected to expressed chimeric alpha 5 cDNA constructs containing the wild-type alpha 5 or the alpha 7A or alpha 7B cytoplasmic domain; all forms of the integrin showed identical activities for adhesion, migration, proliferation, and matrix assembly on fibronectin substrates. These results established that alpha 7 beta 1 receptor can promote myoblast adhesion and motility on a restricted number of laminin isoforms and may be important in myogenic precursor recruitment during regeneration and differentiation.
Yao
C C
CC
Department of Stomatology, School of Dentistry, University of California San Francisco 94143-0512, USA.
Ziober
B L
BL
Sutherland
A E
AE
Mendrick
D L
DL
Kramer
R H
RH
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D016466:CHO Cells; D002448:Cell Adhesion; D002454:Cell Differentiation; D002460:Cell Line; D002465:Cell Movement; D006224:Cricetinae; D003593:Cytoplasm; D006801:Humans; D039001:Integrin alpha Chains; D039482:Integrin alpha5; D007797:Laminin / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics
D015703:Antigens, CD; D039001:Integrin alpha Chains; D039482:Integrin alpha5; D007797:Laminin; D011993:Recombinant Fusion Proteins; C085725:integrin alpha7