Increases in pericellular proteolysis at developing neuromuscular junctions in culture

Abstract

To determine whether localized changes in pericellular proteolysis contribute to synapse formation, we examined the degradative actions of developing Xenopus laevis nerve and muscle cells on films of extracellular matrix proteins adsorbed to the glass surface of a tissue culture chamber. Skeletal myocytes, growing neurites, and fibroblasts all removed fluorescent fibronectin and laminin from the culture substratum at regions of close cell-surface contact. In addition, however, motor neurites also displayed a particularly enhanced rate of gelatin elimination at developing neuromuscular junctions. It has already been shown (a) that there is a similar remodeling of organized muscle basal lamina proteoglycan accumulations along the path of nerve-muscle contact and (b) that this is the earliest detectable biochemical change specific to developing neuromuscular junctions. Our observations thus suggest that the establishment of motoneuron-muscle contact leads to a further activation of pericellular proteinases along both the pre- and the postsynaptic surfaces of the developing junction. We therefore consider whether site-specific proteinase-activation cascades could contribute to the inductive signals that direct synaptic differentiation.