Skeletal Muscle Basement Membrane-Sarcolemma-Cytoskeleton Interaction Minireview Series

Abstract

The sarcolemma (muscle plasma membrane) plays a central role in skeletal muscle structure and function (1). In addition to the housekeeping functions of a cell plasma membrane, the sarcolemma is directly involved in synaptic transmission, action potential propagation, and excitation-contraction coupling (1). Besides these well established physiological functions, the sarcolemma, subsarcolemma cytoskeleton, and surrounding basement membrane (extracellular matrix) play an essential structural role in skeletal muscle (1-3). The biological importance of the basement membrane-sarcolemma-cytoskeleton in skeletal muscle is underscored by the number of inherited muscle diseases caused by mutations in components of the basement membrane, or cytoskeleton, or the sarcolemma protein complexes that link the basement membrane to the cytoskelton (4 -8). The minireview in this and the following issues updates our understanding of the structure and function of the basement membrane, cytoskeletal costameres, and the major trans-sarcolemma links (integrins and dystroglycan) in skeletal muscle.The basement membrane surrounds skeletal muscle fibers and is now known to be critical in muscle fiber structure and function. The skeletal muscle basement membrane is composed of the basal lamina and the reticular lamina. Basal lamina is directly linked to the sarcolemma. Genetic studies of muscular dystrophy patients and animal models of muscular dystrophy have demonstrated the importance of the basement membrane in maintenance of muscle integrity. In addition to maintenance of muscle integrity, the basement membrane is essential in the promotion of myogenesis and muscle development. Muscle regeneration is also a process that depends on the skeletal muscle basement membrane. Satellite cells (endogenous stem cells of skeletal muscle) reside between the muscle fiber and the basal lamina. Following injury, new muscle fibers regenerate within a basement membrane tube, which is believed to act as a mechanical barrier to limit migration of satellite cells, and a scaffold to orient myotube regeneration. Finally, the basement membrane is structurally and functionally specialized in areas of neuromuscular and myotendinous junctions and is required for the assembly of these structures. In the first minireview of this series entitled "The Basement Membrane/ Basal Lamina of Skeletal Muscle," Joshua R. Sanes reviews the structure and function of the skeletal muscle basement membrane. In particular, he focuses on recent molecular studies that have led to a better understanding of the function of the basement membrane in skeletal muscle physiology and pathophysiology (9).A major cytoskeletal structure in muscle that has the unique role of connecting the sarcomere to the basement membrane is the costamere. Costameres were originally described as subsarcolemma protein complexes that align in register with the Z-disk and are physically coupled to the sarcomeres. Costameres may be equivalent to focal adhesions that are expressed in non-muscle cells and are be...

The Dystrophin Glycoprotein Complex

“…Unlike the sarcoglycan subunits, dystroglycan exhibits O-linked glycosylation, and genetic studies have now implicated a novel class of genes in the posttranslational processing of ␣-dystroglycan. 51 Mutations in these genes lead to muscular dystrophy, abnormal central and peripheral nervous system function, as well as cardiomyopathy. Of these novel genes, the fukutin-related protein gene leads to a form of disease that is highly associated with cardiomyopathy.…”

Myogenic Potential of Muscle Side and Main Population Cells after Intravenous Injection into Sub-lethally IrradiatedmdxMice

“…DMD arises from a complete lack or severe absence of dystrophin, a large cytoskeletal protein localized on the cytoplasmic side of the sarcolemma of myofibers (Hoffman et al 1987;Bonilla et al 1988) that is associated with other transmembrane and intracellular proteins in a complex called the dystrophin-associated protein complex (Ervasti et al 1990;Ervasti and Campbell 1991;Ozawa et al 2001). One of the proposed roles of dystrophin within this complex is to provide mechanical support to muscle myofibers during the contraction/relaxation cycle (Ervasti and Campbell 1993;Engel et al 1994;Bushby 1999;Ehmsen et al 2002;Campbell and Stull 2003). Dystrophin deficiency in DMD causes myofiber disruption and ultimately leads to loss of muscle viability and fibrosis.…”

Myopathic changes in murine skeletal muscle lacking synemin

“…Costameres are structures at the sarcolemma of striated muscle fibers that align circumferentially around the Z disks and the M bands of the nearest myofibrils, and longitudinally, to form a rectilinear sarcolemmal network comprised of integral membrane proteins (such as dystroglycan, the sarcoglycans, and Na-K-ATPase), proteins of the extracellular matrix (such as laminin and collagen IV), and proteins of the membraneassociated cytoskeleton (such as dystrophin, syntrophins, spectrin, ankyrin, and vinculin) (12,23,26,41,48,66,71,76,82,87,93,95). Many muscular dystrophies are attributable to mutations in costameric proteins, especially to mutations of proteins of the dystrophin-glycoprotein complex (2,6,10,12,15,27,42,63,74,95).Costameres are linked to the superficial myofibrils of the contractile apparatus by microfilaments, comprised at least in part of ␥-actin (26,43,82), and by IFs, including desmin and several forms of keratin (4,5,7,10,49,54,68,73,88,92). Elimination of these proteins by homologous recombination leads to myopathies.…”