1. Department of Biology, Sinsheimer Laboratories, University of California, Santa Cruz, California 95064, USA

Correspondence to: Yishi Jin Correspondence and requests for materials should be addressed to Y.J. (Email: e-mail: jin@biology.ucsc.edu).

Abstract

At synaptic junctions, specialized subcellular structures occur in both pre- and postsynaptic cells. Most presynaptic termini contain electron-dense membrane structures¹, often referred to as active zones, which function in vesicle docking and release². 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^{3, 4}. 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)^{5, 6}. 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.