The Basement Membrane/Basal Lamina of Skeletal Muscle

Abstract

basement membrane basal lamina acetylcholinesterase acetylcholine receptor muscle-specific kinase Many cells, including skeletal muscle fibers, are coated by a layer of extracellular matrix material called the basement membrane (BM).1 The BM, in turn, is composed of two layers: an internal, felt-like basal lamina (BL) directly linked to the plasma membrane, and an external, fibrillar reticular lamina. BMs contain protein and carbohydrate but no lipid or nucleic acid. Virtually all the protein is glycosylated, and nearly all the carbohydrate is covalently bound to protein. The fibrils of the reticular lamina are collagenous, and they are embedded in an amorphous proteoglycan-rich ground substance. The BL contains non-fibrillar collagen, non-collagenous glycoproteins, and proteoglycans (1Timpl, R., and Rohrbach, O. (eds) Molecular and Cellular Aspects of Basement Membranes, Academic Press, New York.Google Scholar). Initially, the BM was viewed as a static structure that provides mechanical support; essentially something for the cells to sit on. A key advance was the discovery that, because the acellular BM survives injury to associated cells, it can provide a scaffold to orient and constrain cells during regeneration (2Vracko R. Benditt E.P. J. Cell Biol. 1972; 55: 406-419Crossref PubMed Scopus (276) Google Scholar). A more radical transformation over the past few decades was the realization that BM components play active roles and that these roles extend to developmental as well as regenerative processes (1Timpl, R., and Rohrbach, O. (eds) Molecular and Cellular Aspects of Basement Membranes, Academic Press, New York.Google Scholar). In skeletal muscle, these processes include myogenesis and synaptogenesis. Most recently, emphasis has shifted to a search for the matrix-associated signals and membrane-associated receptors that underlie cell-matrix interactions. The purpose of this minireview is to relate results from the new molecular analyses to the early cellular observations that motivated them. For more detailed descriptions of what happened in between, see Refs. 3Sanes J.R. Engel A.G. Franzini-Armstrong C. Mycology. McGraw Hill, New York1994: 242-260Google Scholar, 4Sanes J.R. Semin. Dev. Biol. 1995; 6: 163-173Crossref Scopus (28) Google Scholar, 5Sanes J.R. Lichtman J.W. Annu. Rev. Neurosci. 1999; 22: 389-442Crossref PubMed Scopus (1209) Google Scholar. Although we now know that BMs are present in nearly all tissues, their existence was first appreciated in muscle. In his 1840 report “On the Minute Structure and Movements of Voluntary Muscle,” Bowman (6Bowman W. Philos. Trans. R. Soc. Lond. Biol. Sci. 1840; 130: 457-494Crossref Google Scholar) described a “highly delicate, transparent, and probably elastic” sheath encircling individual muscle fibers. This sheath, which he called the sarcolemma, became apparent when muscle fibers were injured during dissection; the cell itself lysed and retracted, leaving the sarcolemma behind (Fig.1). Over a century later, electron microscopy revealed that the BM is the main component of such tubes and that the BL is a main component of the BM. Today the term sarcolemma is often used to refer to the plasma membrane alone, although only fragments of it were present in Bowman's tubes (3Sanes J.R. Engel A.G. Franzini-Armstrong C. Mycology. McGraw Hill, New York1994: 242-260Google Scholar). The terms BL and BM are often used interchangeably, but should not be; I will attempt to use them appropriately here. Bowman's view of what we now know to be BM and particularly his evidence for its “strength and tenacity” (6Bowman W. Philos. Trans. R. Soc. Lond. Biol. Sci. 1840; 130: 457-494Crossref Google Scholar) led directly to appreciation of its role in muscle function. Muscles are strong, flexible, and stress-resistant. Formal models of their mechanical properties include both contractile and elastic elements. The contractile element is, of course, the sarcomere, and extracellular matrix accounts for much of the elasticity. In fact, several matrix-rich structures contribute to muscle strength and elasticity, but a sizable fraction has been shown to reside in the BM (7Tidball J.G. Biophys. J. 1986; 50: 1127-1138Abstract Full Text PDF PubMed Scopus (35) Google Scholar). Direct biophysical analysis of BM is lacking, but keys to its strength most likely are its major structural components (8Timpl R. Brown J.C. Bioessays. 1996; 18: 123-132Crossref PubMed Scopus (575) Google Scholar, 9Colognato H. Yurchenco P.D. Dev. Dyn. 2000; 218: 213-234Crossref PubMed Scopus (1024) Google Scholar). The most abundant protein of the BL is triple-helical collagen IV, the subunits of which, called α chains, have prominent terminal non-collagenous domains. The major non-collagenous protein is laminin, which is also a heterotrimer of related chains, in this case called α, β, and γ. Both collagens IV and laminins exist in multiple isoforms, with the most abundant in muscle being collagen (α1(IV))2(α2(IV))1