Retrograde signaling in the formation and maintenance of the neuromuscular junction

The neuromuscular junction is characterized by precise alignment between the nerve terminal an the postsynaptic apparatus formed by the muscle fiber. Organization of the neuromuscular junction during embryonic development, growth, and maintenance is coordinated by signals exchanged between motor neurons and their target muscel fibers. Identification of proteins such as agrin, likely to represent neuronal agents that direct the organization of the postsynaptic apparatus, has focused attention on characterization of proteins that mediate retrograde signals that regualte the organization and function of the nerve terminal. The results of these studies implicate a role for both adhesive and diffusible signal in coordinating the development, maturation, and maintenance of the motor nerve terminal. The diversity of molecules identified to date that appear to play a role in these processes implies a considerable level of redundancy in the transduction pathway. However, studies of early nerve-muscle interactions suggest that a common feature of many of these retrograde agents is activation of a protein kinase coupled with and increase in cytosolic Ca²⁺ concentration. While the molecular signals that regulate growth and maintenance of neuromuscular junctions are less well understood it seems likely that similar adhesive and diffusible factor will be involved. 1994 John Wiley & Sons, Inc.