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Article
Nature Neuroscience - 9, 1479 - 1487 (2006)
Published online: 19 November 2006; | doi:10.1038/nn1808

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

Ya Dai1, 2, Hidenori Taru1, Scott L Deken3, Brock Grill1, Brian Ackley1, Michael L Nonet3 & Yishi Jin1, 2

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

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

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

Correspondence should be addressed to Yishi Jin jin@biology.ucsc.edu

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-alpha, bind each other and are implicated in linking active zone formation to synaptic vesicle release. Loss of function in Caenorhabditis eleganssyd-2 Liprin-alpha 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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Nature Neuroscience
ISSN: 1097-6256
EISSN: 1546-1726
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