Clarinet (CLA-1), a novel active zone protein required for synaptic vesicle clustering and release
- Yale University, United States
- University of Illinois at Chicago, United States
- Stanford University, United States
Abstract
Active zone proteins cluster synaptic vesicles at presynaptic terminals and coordinate their release. In forward genetic screens we isolated a novel C. elegans active zone gene, clarinet (cla-1). cla-1 mutants exhibit defects in synaptic vesicle clustering, active zone structure and synapse number. As a result, they have reduced spontaneous vesicle release and increased synaptic depression. cla-1 mutants show defects in vesicle distribution near the presynaptic dense projection, with fewer undocked vesicles contacting the dense projection and more docked vesicles at the plasma membrane. cla-1 encodes 3 isoforms containing common C-terminal PDZ and C2 domains with homology to vertebrate active zone proteins Piccolo and RIM. The C-termini of all isoforms localize to the active zone. Specific loss of the ~9000 amino acid long isoform results in vesicle clustering defects and increased synaptic depression. Our data indicate that specific isoforms of clarinet serve distinct functions, regulating synapse development, vesicle clustering and release.
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Author details
Funding
National Institutes of Health (R01NS076558)
- Zhao Xuan
- Jessica Nelson
- Daniel A Colón-Ramos
Howard Hughes Medical Institute (Investigator)
- Kang Shen
- Peri T Kurshan
National Institutes of Health (5R01NS048392)
- Kang Shen
- Peri T Kurshan
National Science Foundation (NSF IOS 1353845)
- Zhao Xuan
- Jessica Nelson
- Daniel A Colón-Ramos
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2017, Xuan et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Clarinet (CLA-1), a novel active zone protein required for synaptic vesicle clustering and release
eLife 6:e29276.
https://doi.org/10.7554/eLife.29276
