Plasminogen activators and inhibitors in the neuromuscular system: III. The serpin protease nexin I is synthesized by muscle and localized at neuromuscular synapses

• Published in: Journal of cellular physiology Vol. 147; no. 1; p. 76
• Main Authors: Festoff, B W, Rao, J S, Hantaï, D
• Format: Journal Article
• Language: English
• Published: United States 01.04.1991
• Subjects: Amyloid beta-Protein Precursor; Animals; Blotting, Western; Carrier Proteins - immunology; Carrier Proteins - metabolism; Cells, Cultured; Fluorescent Antibody Technique; Humans; In Vitro Techniques; Mice; Muscles - enzymology; Neuromuscular Junction - enzymology; Neuromuscular Junction - ultrastructure; Plasminogen Activators - physiology; Plasminogen Inactivators - metabolism; Protease Nexins; Receptors, Cell Surface; Receptors, Nicotinic - immunology; Receptors, Nicotinic - metabolism; Serpins - metabolism
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041470111

Recent studies suggest that the nature of events leading to the formation, maintenance, and elimination of synapses may be regulated by cascade-type, locally expressed proteases and protease inhibitors acting on adhesive extracellular matrix components. We have identified a molecule in conditioned medium of murine skeletal muscle cells that in molecular weight, target protease inhibition, heparin-binding and cross-reactivity with authenic antisera is similar to the human serine proteinase inhibitor, protease nexin I. Protease nexin I is a 43-50 kDa glycoprotein of the serpin superfamily (arg-serpin class). Purified anti-protease nexin I antibody (anti-47 kDa) stains adult mouse skeletal muscle in discrete foci that precisely superimpose on synaptic neuromuscular junctions. Protease nexin I appears in patches on surfaces of cultured mouse skeletal myotubes, but not on myoblasts. These patches co-localize with acetylcholine receptor clusters and acetylcholinesterase staining during cellular maturation in culture. Evidence that protease nexin I is a synaptic, extracellular antigen is particularly intriguing since it has been shown to be identical, in structure and activity, with a factor released by glial cells, called glia-derived nexin that stimulates mouse neuroblastoma cell neurite outgrowth and inhibits granule cell migration. Protease nexin I inhibits both tumor cell and myoblast plasminogen activator-mediated destruction of extracellular matrix. Thus, such observations as presented in this report provide further evidence for involvement of cascade proteolytic systems, and their post-translational regulation by specific serpins, in the remodeling that occurs in synapse formation and elimination.