Agrin neuromuscular junction

Fig. 20.8. Neuromuscular junctions analyzed by transmission electron microscopy. (A) In wild-type mice, the motor nerve terminal (MN) is depressed into the muscle fiber surface. The terminal is polarized, with small clear vesicles near the presynaptic membrane and mitochondria in the more proximal portion of the terminal. The postsynaptic membrane has deep convolutions (junctional folds, JF) and the membrane near the tops of these folds is very electron dense because of the high density of acetylcholine receptors (arrowheads). (B) In some myasthenias where the nerve sprouts but remains in contact with the muscle, terminals with mitochondria and vesicles are observed in the absence of any postsynaptic specialization. Presumably these are sprouting terminals that have not established a functional connection. (C) Partial innervation of postsynaptic sites is evident as elaborate junctional folds in the muscle membrane with no overlying nerve terminal. In these examples, the interpretations were aided by light microscopy examination of other samples as described in Fig. 20.8 in parallel with electron microscopy. The mutation shown in (B, C) is an unpublished ENU-induced allele of agrin.

By the time of innervation at G16, the acetylcholine receptors (AChRs) which had been scattered along the length of the immature muscle fibers, cluster at the areas which will become the neuromuscular junction (Anderson and Cohen, 1977), a phenomenon that is at least partially dependent upon the release of agrin from the approaching axon terminal (McMahan et al., 1980). 

Agrin appears to direct the aggregation of AChRs at both developing and regenerating neuromuscular Junctions (see review by Hall and Sanes, 1993). 

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