The Agrin Hypothesis
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Excerpt
The surface of the muscle fiber at vertebrate neuromuscular junctions is characterized by aggregates of molecules and organelles that, altogether, comprise the postsynaptic apparatus. Some of these aggregates play a direct role in synaptic transmission and thus are crucial for neuromuscular function. For example, the plasma membrane of the muscle fiber has aggregates of receptors (AChRs) for the neurotransmitter, acetylcholine, whereas the basal lamina of the myofiber has a high concentration of acetylcholinesterase (AChE).
During the last 20 years, considerable effort has been devoted to understanding how the postsynaptic apparatus forms in the embryo, how it is regulated in the adult, and how it reforms during regeneration. One finding from these studies is that the formation and maintenance of the postsynaptic apparatus is dependent on molecules provided by the axon (for review, see Dennis 1981). Studies conducted in my laboratory have led to the hypothesis that agrin, a protein we...
