The Drosophila Larval Neuromuscular Junction as a Model for Scaffold Complexes at Glutamatergic Synapses: Benefits and Limitations

Based on unbeatable genetic accessibility and relative simplicity, the Drosophila larval neuromuscular junction has become a widely used model system for studying functional and structural aspects of excitatory glutamatergic synapses. Membrane-associated guanylate kinasc-like proteins (MAGUKs) are first-order scaffolding molecules enriched at many cellular junctions, including synapses, where they coordinate multiple binding partners, including cell adhesion molecules and ion channels. The enrichment of the prototypic MAGUK Discs-Large at larval NMJs apparently parallels the high abundance of its homologs at excitatory synapses in the mammalian central nervous system. Here, the authors review selected aspects of the long-standing work on Dig at fly neuromuscular junctions, thereby scrutinizing its subcellular localization, function, and regulation with regard to corresponding aspects of MAGUKs in vertebrate neurons.