Matrix metalloproteinase-3 removes agrin from synaptic basal lamina

Michael VanSaun, Michael J. Werle

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

Agrin, a heparin sulfate proteoglycan, is an integral member of the synaptic basal lamina and plays a critical role in the formation and maintenance of the neuromuscular junction. The N-terminal region of agrin binds tightly to basal lamina, while the C-terminal region interacts with a muscle-specific tyrosine kinase (MuSK) to induce the formation of the postsynaptic apparatus. Although the binding of agrin to basal lamina is tight, the binding of agrin to MuSK has yet to be shown; therefore, basal lamina binding is critical for maintaining the presentation of agrin to MuSK. Here we report evidence that supports our hypothesis that matrix metalloproteinase-3 (MMP-3) is responsible for the removal of agrin from synaptic basal lamina. Antibodies to the hinge region of human MMP-3 recognize molecules concentrated at the frog neuromuscular junction in both cross sections and whole mounts. Electron microscopy of neuromuscular junctions stained with antibodies to MMP-3 reveals that staining is found in the extracellular matrix surrounding the Schwann cell. Treatment of sections from frog anterior tibialis muscle with MMP-3 results in a clear and reproducible removal of agrin immunoreactivity from synaptic basal lamina. The same MMP-3 treatment does not alter anti-laminin staining. These results support our hypothesis that synaptic activity results in the activation of MMP-3 at the neuromuscular junction and that MMP-3 specifically removes agrin from synaptic basal lamina. (C) 2000 John Wiley and Sons, Inc.

Original languageEnglish (US)
Pages (from-to)140-149
Number of pages10
JournalJournal of Neurobiology
Volume43
Issue number2
DOIs
StatePublished - 2000
Externally publishedYes

Keywords

  • Agrin
  • Matrix metalloproteinase-3
  • Neuromuscular junction
  • Schwann cell
  • Synapse elimination

ASJC Scopus subject areas

  • Neuroscience(all)
  • Cellular and Molecular Neuroscience

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