1. Cell Biology
  2. Neuroscience
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Clarinet (CLA-1), a novel active zone protein required for synaptic vesicle clustering and release

  1. Zhao Xuan
  2. Laura Manning
  3. Jessica Nelson
  4. Janet E Richmond
  5. Daniel A Colón-Ramos
  6. Kang Shen
  7. Peri T Kurshan  Is a corresponding author
  1. Yale University, United States
  2. University of Illinois at Chicago, United States
  3. Stanford University, United States
Research Article
  • Cited 18
  • Views 3,337
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Cite this article as: eLife 2017;6:e29276 doi: 10.7554/eLife.29276

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.

Article and author information

Author details

  1. Zhao Xuan

    Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University, New Haven, United States
    Competing interests
    No competing interests declared.
  2. Laura Manning

    Department of Biological Sciences, University of Illinois at Chicago, Chicago, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1597-0600
  3. Jessica Nelson

    Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University, New Haven, United States
    Competing interests
    No competing interests declared.
  4. Janet E Richmond

    Department of Biological Sciences, University of Illinois at Chicago, Chicago, United States
    Competing interests
    No competing interests declared.
  5. Daniel A Colón-Ramos

    Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University, New Haven, United States
    Competing interests
    No competing interests declared.
  6. Kang Shen

    Department of Biology, Stanford University, Stanford, United States
    Competing interests
    Kang Shen, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4059-8249
  7. Peri T Kurshan

    Department of Biology, Stanford University, Stanford, United States
    For correspondence
    pkurshan@stanford.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6267-7103

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.

Reviewing Editor

  1. Graeme W Davis, University of California, San Francisco, United States

Publication history

  1. Received: June 4, 2017
  2. Accepted: November 20, 2017
  3. Accepted Manuscript published: November 21, 2017 (version 1)
  4. Version of Record published: December 13, 2017 (version 2)

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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