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SYD-2 Liprin-α organizes presynaptic active zone formation through ELKS

Nature Neuroscience volume 9, pages 1479–1487 (2006)Cite this article

Abstract

A central event in synapse development is formation of the presynaptic active zone in response to positional cues. Three active zone proteins, RIM, ELKS (also known as ERC or CAST) and Liprin-α, bind each other and are implicated in linking active zone formation to synaptic vesicle release. Loss of function in Caenorhabditis eleganssyd-2 Liprin-α alters the size of presynaptic specializations and disrupts synaptic vesicle accumulation. Here we report that a missense mutation in the coiled-coil domain of SYD-2 causes a gain of function. In HSN synapses, the syd-2(gf) mutation promotes synapse formation in the absence of syd-1, which is essential for HSN synapse formation. syd-2(gf) also partially suppresses the synaptogenesis defects in syg-1 and syg-2 mutants. The activity of syd-2(gf) requires elks-1, an ELKS homolog; but not unc-10, a RIM homolog. The mutant SYD-2 shows increased association with ELKS. These results establish a functional dependency for assembly of the presynaptic active zone in which SYD-2 plays a key role.

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Figure 1: syd-2 (ju487) suppresses egg-laying and HSN synapse defects of syd-1(lf).
Figure 2: syd-2(ju487gf) alters a conserved arginine in the coiled-coil domain of Liprin-α and is normally expressed and localized.
Figure 3: Synaptic localization of endogenous active zone proteins.
Figure 4: elks-1 is required for the suppression of syd-1 by syd-2(ju487gf) and SYD-2(R184C) shows increased association with ELKS-1.
Figure 5: syd-2(ju487gf) partially suppresses HSN synapse targeting defects in syg-1 and syg-2 mutants.

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Acknowledgements

We thank K. Shen (Stanford University) for kyIs235 marker, Punc-86GFP plasmid and for communicating unpublished data, A.D. Chisholm for advice on genetics and statistic analysis, the National Bioresource project for the Experimental Animal C. elegans for elks-1(tm1233), T. Ishihara (Kyushu University) for VenusGFP vector, J. McEwan and J. Kaplan (Massachusetts General Hospital) for Pttx-3-RFP and Pttx-3-GFP plasmids, and the members of the Jin and Chisholm labs for discussions. This work was supported by grants from the US National Institutes of Health to Y.J. and M.N., postdoctoral fellowships from Japanese Society for Promoting Science and the Uehara Memorial Foundation to H.T., a Canadian CIHR fellowship to B.G., and a Career Development Award from the Muscular Dystrophy Association to B.A. Y.D. is an research associate, and Y.J. is an investigator, of the Howard Hughes Medical Institute.

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Authors and Affiliations

  1. Department of Molecular, Cell and Developmental Biology, Sinsheimer Laboratories, University of California, 1156 High Street, Santa Cruz, 95064, California, USA

    Ya Dai, Hidenori Taru, Brock Grill, Brian Ackley & Yishi Jin

  2. Howard Hughes Medical Institute, University of California, 1156 High Street, Santa Cruz, 95064, California, USA

    Ya Dai & Yishi Jin

  3. Department of Anatomy and Neurobiology, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, Missouri, 63110, USA

    Scott L Deken & Michael L Nonet

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Contributions

Y.D., H.T. and Y.J. designed and Y.D. and H.T. performed the experiments, others provided reagents and contributed to data analysis, and Y.D. and Y.J. wrote the manuscript.

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Correspondence to Yishi Jin.

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Supplementary information

Supplementary Fig. 1

SYD-1 and its mouse homologs. (PDF 488 kb)

Supplementary Fig. 2

Expression of SYD-2 in muscles cells is not affected in syd-1 mutants. (PDF 2461 kb)

Supplementary Fig. 3

Expression of UNC-10/RIM is not altered in syd-2(ju487gf). (PDF 970 kb)

Supplementary Fig. 4

Expression of SYD-1::GFP is not altered in syd-2, unc-10, or elks-1. (PDF 386 kb)

Supplementary Fig. 5

Summary of the genetic interactions between syd and syg genes in HSN synapses. (PDF 151 kb)

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Dai, Y., Taru, H., Deken, S. et al. SYD-2 Liprin-α organizes presynaptic active zone formation through ELKS. Nat Neurosci 9, 1479–1487 (2006). https://doi.org/10.1038/nn1808

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