Matrix metalloproteinases (Mmps) and their inhibitors (Timps) are thought to be important for synaptogenesis, but their roles are poorly understood – at least in part because there is significant complexity and redundancy in the mammalian matrix metalloproteome. Kendal Broadie and colleagues (p. ) have therefore turned to Drosophila, which have just two Mmps and a single Timp, as a simpler system to assess the roles of Mmps and Timps at the developing neuromuscular junction (NMJ). They find that depletion of either mmp1 or mmp2 alone leads to increased synaptic architectural complexity as well as elevated functional neurotransmission. Surprisingly, however, simultaneous loss of both Mmps or overexpression of Timp, has a much weaker phenotype. It appears to be the balance of Mmp1 and Mmp2 on both pre- and postsynaptic sides of the NMJ that is critical for appropriate synapse formation. The authors find no ultrastructural defects, but rather that dysregulation of Mmp activity impacts synaptic Wnt signalling, with the level and localisation of the Wnt co-receptor Dlp impaired in Mmp mutants. Although the precise roles of and the interplay between Mmp1, Mmp2 and Timp have yet to be fully understood, this system provides a powerful new model for investigating the roles of the matrix metalloproteome during synaptogenesis.
