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Synapse-forming axons and recombinant agrin induce microprocess formation on myotubes
1Laboratory of Biochemical Genetics, National Heart, Lung, and Blood Institute, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-4036, USA.
Summary
Axons induce muscle cell surface motility during synapse formation, with agrin signaling playing a key role in initiating neuromuscular junction development.
Area of Science:
- Neuroscience
- Cell Biology
- Developmental Biology
Background:
- Synaptogenesis involves intricate cell-surface interactions between neurons and muscle cells.
- Understanding the molecular mechanisms driving these interactions is crucial for comprehending neuromuscular junction formation.
Purpose of the Study:
- To investigate cell-surface dynamics at developing nerve-muscle contacts during synaptogenesis.
- To explore the role of agrin in mediating muscle cell surface motility and synapse formation.
Main Methods:
- Coculture of rat ventral spinal cord (VSC) neurons and myotubes.
- Transmission and scanning electron microscopy to examine cell-surface structures.
- Functional assays using recombinant agrin and transfected myotubes.
Main Results:
- Myotube surfaces at sites of axon contact exhibited increased motility, including ruffles and microprocesses, unlike contacts with neuronal somata or dendrites.
- Axon contacts showed closer membrane apposition, suggesting stronger adhesion.
- Agrin treatment rapidly induced microprocess formation in myotubes, mimicking events at developing synapses.
Conclusions:
- Muscle cell surface motility and adhesion are polarized during synaptogenesis, with axons playing a distinct role.
- Agrin signaling is implicated in inducing muscle cell surface motility, potentially initiating neuromuscular junction formation.