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Publication : Alternatively spliced isoforms of nerve- and muscle-derived agrin: their roles at the neuromuscular junction.

First Author  Burgess RW Year  1999
Journal  Neuron Volume  23
Issue  1 Pages  33-44
PubMed ID  10402191 Mgi Jnum  J:55407
Mgi Id  MGI:1337916 Doi  10.1016/s0896-6273(00)80751-5
Citation  Burgess RW, et al. (1999) Alternatively spliced isoforms of nerve- and muscle-derived agrin: their roles at the neuromuscular junction. Neuron 23(1):33-44
abstractText  Agrin induces synaptic differentiation at the skeletal neuromuscular junction (NMJ); both pre- and postsynaptic differentiation are drastically impaired in its absence. Multiple alternatively spliced forms of agrin that differ in binding characteristics and bioactivity are synthesized by nerve and muscle cells. We used surgical chimeras, isoform-specific mutant mice, and nerve-muscle cocultures to determine the origins and nature of the agrin required for synaptogenesis. We show that agrin containing Z exons (Z+) is a critical nerve-derived inducer of postsynaptic differentiation, whereas neural isoforms containing a heparin binding site (Y+) and all muscle-derived isoforms are dispensable for major steps in synaptogenesis. Our results also suggest that the requirement of agrin for presynaptic differentiation is mediated indirectly by its ability to promote postsynaptic production or localization of appropriate retrograde signals.
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