Early in the development of neuromuscular junctions (NMJs) – specialised synapses between the axon terminals of motoneurons and a receptor-rich postsynaptic apparatus of the muscle fibre membrane – the nerve-derived proteoglycan agrin organises and stabilises plaque-like postsynaptic clusters of acetylcholine receptors. These plaques are subsequently converted into pretzel-like structures that contain central receptor-free areas. So, ask Peter Sonderegger and colleagues (p. ), does agrin's NMJ-promoting and stabilising function have to be reduced during NMJ maturation? The authors show that transgenic overexpression of neurotrypsin (a neuronal serine protease that cleaves agrin at two sites) in mouse motoneurons results in excessive reorganisation and dispersal of NMJs. By contrast, they report, expression of cleavage-resistant agrin in motoneurons slows down NMJ remodelling and maturation. The authors propose, therefore, that agrin-dependent stabilisation of the NMJ has to be relieved by the proteolytic degradation of agrin for the plaque-to-pretzel maturation of the NMJ to proceed. Notably, however, NMJ maturation is normal in neurotrypsin-dependent mice. Thus, an unidentified protease rather than neurotrypsin must be involved in endplate reorganisation during NMJ maturation.
