Perlecan antagonizes collagen IV and ADAMTS9/GON-1 in restricting the growth of presynaptic boutons.

In the mature nervous system, a significant fraction of synapses are structurally stable over a long time scale. However, the mechanisms that restrict synaptic growth within a confined region are poorly understood. Here, we identified that in the C. elegans neuromuscular junction, collagens Type IV and XVIII, and the secreted metalloprotease ADAMTS/GON-1 are critical for growth restriction of presynaptic boutons. Without these components, ectopic boutons progressively invade into the nonsynaptic region. Perlecan/UNC-52 promotes the growth of ectopic boutons and functions antagonistically to collagen Type IV and GON-1 but not to collagen XVIII. The growth constraint of presynaptic boutons correlates with the integrity of the extracellular matrix basal lamina or basement membrane (BM), which surrounds chemical synapses. Fragmented BM appears in the region where ectopic boutons emerge. Further removal of UNC-52 improves the BM integrity and the tight association between BM and presynaptic boutons. Together, our results unravel the complex role of the BM in restricting the growth of presynaptic boutons and reveal the antagonistic function of perlecan on Type IV collagen and ADAMTS protein.