Basement membrane (BMs) of the neuromuscular system. (A) Electron microscopy of BMs in normal diaphragm muscle (SM, skeletal muscle). Red arrow = BM, blue arrow = sarcolemma, yellow arrowhead = sarcomere (cross-section), green arrowhead = collagen fibrils in the interstitial matrix (ECM). (B) Scheme of the motor innervation with distinct BMs. The BMs comprise a continuous layer around muscle fibers and Schwann cells of the peripheral nervous system (red layer), and there is a different composition of laminin chains and other extracellular matrix components at the neuromuscular junction (NMJ) (yellow layer). Muscle fibers and satellite cells are surrounded by an extrasynaptic BM containing mainly laminin-211. At the NMJ, laminins 221, 421 and 521 are the prominent laminin isoforms. Schwann cells at the NMJ and myelinating Schwann cells (blue = myelin) that frame the axon of the motor nerve are surrounded by a BM with slightly different laminin composition (laminins 211 and 411 as well as 221 and 421). (C) Laminin α2 chain expression in BMs of the neuromuscular system (immunofluorescent staining with the 4H8-2 antibody generated against the N-terminal domain of the laminin α2 chain). The laminin α2 subunit (red staining) forms the backbone of BMs that surround muscle fibers (extrasynaptic BMs) (purple arrow),underlie the NMJ (yellow) (the co-localization of laminin α2 chain (red staining) and acetylcholine receptors (green staining with α-bungarotoxin) is also shown), surround Schwann cells of the intramuscular peripheral nerve (blue arrow), surround muscle spindles (white arrowhead) and underlie the myotendinous junction (MTJ) (white arrows). Inset shows a higher magnification of the MTJ.