Loss of basement membrane, receptor and cytoskeletal lattices in a laminin-deficient muscular dystrophy

Abstract

Basement membrane laminins bearing the α2-subunit interact with α-dystroglycan and β1-integrins, cell-surface receptors that are found within the rectilinear costameric lattices of skeletal muscle sarcolemma. Mutations of the α2 subunit are a major cause of congenital muscular dystrophy. To determine whether the costameres are altered as a result of laminin α2-mutations, the skeletal muscle surface of a dystrophic mouse (dy2J/dy2J) lacking the α2-LN domain was examined by confocal and widefield deconvolution immunomicroscopy. Although the dy2J dystrophic fibers possessed a normal-appearing distribution of α2-laminins and α-dystroglycan within a rectilinear costameric lattice at 6.5 weeks of age, by 11 weeks the surface architecture of these components were found to be disorganized, with frequent effacement of the circumferential and longitudinal lattice striations. The defect in the lattice organization was also noted to be a characteristic of type IV collagen, nidogen, perlecan, β1D-integrin, dystrophin and vinculin. The development of this pattern change occurring only after birth suggests that although α2-laminins are not essential for the initial assembly of the costameric framework, they play a role in maintaining the stability and organization of the framework.