SYD-2 Liprin-α organizes presynaptic active zone formation through ELKS
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-alpha, bind each other and are implicated in linking active zone formation to synaptic vesicle release. Loss of function in Caenorhabditis elegans syd-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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α-Liprin is required for active zone formation with recruitment of synaptic vesicles and of LAR-type receptor phosphotyrosine phosphatases.
“Together, these data established that active zone formation with recruitment of synaptic vesicles and of LAR-type receptor phosphotyrosine phosphatases requires α-liprin, possibly by simultaneous binding of α-liprin to the receptor phosphotyrosine phosphatase, RIM, ELKS, Syd-1, and itself.”
From The Presynaptic Active Zone (2012) · cites this paper as Dai et al., 2006
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- Authors
- Dai, Y., Taru, H., Deken, S. L., Grill, B., Ackley, B., Nonet, M. L., & Jin, Y.
- Affiliations
- University of California, Santa Cruz (US)
- Washington University in St. Louis (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Jin, Yishi
- Venue
- Nature Neuroscience
- Published
- 2006-11-19
- Volume
- 9
- Issue
- 12
- Pages
- 1479-1487
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- OpenAlex
- W1999369847
- Cited by
- 218
- References
- 41
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 15 · 2023: 14 · 2022: 8 · 2021: 7 · 2020: 14 · 2019: 10 · 2018: 11 · 2017: 8 · 2016: 14 · 2015: 12 · 2014: 14 · 2013: 16 · 2012: 10
- FWCI
- 3.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Keywords
- Liprin-α, active zone, elk, RIM, synaptogenesis, Caenorhabditis elegans, coiled-coil domain, gain-of-function mutations
- MeSH terms
- Animals, Carrier Proteins, Cytoskeleton, Gene Expression Regulation, Motor Neurons, Mutation, Synaptic Transmission, Phosphoproteins, Synaptic Vesicles, Caenorhabditis elegans, Presynaptic Terminals, Caenorhabditis elegans Proteins, Animals, Genetically Modified, Intercellular Signaling Peptides and Proteins, Intracellular Signaling Peptides and Proteins
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