The liprin protein SYD-2 regulates the differentiation of presynaptic termini in C. elegans

At synaptic junctions, specialized subcellular structures occur in both pre- and postsynaptic cells. Most presynaptic termini contain electron-dense membrane structures, often referred to as active zones, which function in vesicle docking and release. The components of those active zones and how they are formed are largely unknown. We report here that a mutation in the Caenorhabditis elegans syd-2 (for synapse-defective) gene causes a diffused localization of several presynaptic proteins and of a synaptic-vesicle membrane associated green fluorescent protein (GFP) marker. Ultrastructural analysis revealed that the active zones of syd-2 mutants were significantly lengthened, whereas the total number of vesicles per synapse and the number of vesicles at the prominent active zones were comparable to those in wild-type animals. Synaptic transmission is partially impaired in syd-2 mutants. syd-2 encodes a member of the liprin (for LAR-interacting protein) family of proteins which interact with LAR-type (for leukocyte common antigen related) receptor proteins with tyrosine phosphatase activity (RPTPs). SYD-2 protein is localized at presynaptic termini independently of the presence of vesicles, and functions cell autonomously. We propose that SYD-2 regulates the differentiation of presynaptic termini in particular the formation of the active zone, by acting as an intracellular anchor for RPTP signalling at synaptic junctions.