Laminin-alpha2 but not -alpha1-mediated adhesion of human (Duchenne) and murine (mdx) dystrophic myotubes is seriously defective.
It has been suggested that alpha-dystroglycan links the dystrophin-associated protein complex and extracellular matrix and that the absence of dystrophin and alpha-dystroglycan in Duchenne muscular dystrophy (DMD) may lead to the breakdown of this linkage. In the present study, myotubes from DMD patients and murine X-linked muscular dystrophic mice (mdx) were used to measure their adhesive force to the physiological laminin-alpha2 substrate, and it was found that the dystrophic myotubes were selectively unable to sustain adhesion. However, normal and dystrophic myotubes attached equally well to the laminin-alpha1 substrate. As far as we know, this is the first experimental evidence that the absence of dystrophin causes the complete loss of a still unknown laminin-alpha2-dependent adhesion force, therefore suggesting that the primary consequence of Duchenne dystrophy consists of the loss of an authentic mechanical linkage at the level of the alpha-dystroglycan/basal lamina interface.
Angoli
D
D
Department of General Physiology and Biochemistry, University of Milan, Italy.
Corona
P
P
Baresi
R
R
Mora
M
M
Wanke
E
E
D000818:Animals; D002448:Cell Adhesion; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000502:physiology; D049030:Dystroglycans; D005109:Extracellular Matrix / Q000502:physiology; D006801:Humans; D007797:Laminin / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D018101:Mice, Inbred mdx; D018485:Muscle Fibers, Skeletal / Q000502:physiology*; D018482:Muscle, Skeletal / Q000502:physiology / Q000503:physiopathology*; D009136:Muscular Dystrophies / Q000503:physiopathology*; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000503:physiopathology*; D017474:Receptors, Laminin / Q000502:physiology; D012016:Reference Values; D013314:Stress, Mechanical; D014960:X Chromosome
D003598:Cytoskeletal Proteins; C483081:DAG1 protein, human; D007797:Laminin; D008562:Membrane Glycoproteins; D017474:Receptors, Laminin; C102645:laminin alpha 2; D049030:Dystroglycans; C084098:laminin A