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

Nature volume 401, pages 371–375 (1999)Cite this article

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) marker3,4. 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.

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Figure 1: syd-2(ju37) causes diffuse localization of a synaptic-vesicle GFP marker.
Figure 2: syd-2 encodes a liprin.
Figure 3: SYD-2 is localized to presynaptic regions.
Figure 4: Presynaptic active zones were lengthened in syd-2(ju37) animals.
Figure 5: Pharmacological responses of syd-2(ju37) animals.

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Acknowledgements

We thank M. Nonet for SNB-1::GFP DNA and antibodies for SNT-1, SNB-1, syntaxin and RAB-3; Y. Kohara for the yk100c11 clone; A. Fire for the GFP vectors; M. Han for the pTG96 plasmid; C. elegans genome consortium for the sequence and clone of cosmid F59F5; A. Chisholm, E. Jorgensen and M. Nonet for helpful discussion throughout this work; E. Hartwieg for teaching us electron micrograph analysis; and R. Horvitz for his generosity. A. Chisholm, J. Kaplan, G. Garriga, L. Hinck, A. Zahler, R. Baran, Y. Ho and members of the Chisholm and Jin laboratories made comments on this paper. Some strains used in this work were obtained from the Caenorhabditis elegans Genetics Center, which is funded by NIH Center for research resources. M.Z. is supported by a Human Frontier Science Program Long Term Postdoctoral Fellowship. Y.J. is a Alfred P. Sloan research fellow. This work was supported by US PHS research grant NS35546 to Y.J. The GenBank accession numbers for syd-2 genomic DNA and cDNA are Z50794 and AF170122, respectively.

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

    Mei Zhen & Yishi Jin

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Correspondence to Yishi Jin.

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Zhen, M., Jin, Y. The liprin protein SYD-2 regulates the differentiation of presynaptic termini in C. elegans. Nature 401, 371–375 (1999). https://doi.org/10.1038/43886

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