Clarinet (CLA-1), a novel active zone protein required for synaptic vesicle clustering and release
Active zone proteins cluster synaptic vesicles at presynaptic terminals and coordinate their release. In forward genetic screens, we isolated a novel Caenorhabditis elegans active zone gene, clarinet (cla-1). cla-1 mutants exhibit defects in synaptic vesicle clustering, active zone structure and syn...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2017-11-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/29276 |
| _version_ | 1828166908140060672 |
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| author | Zhao Xuan Laura Manning Jessica Nelson Janet E Richmond Daniel A Colón-Ramos Kang Shen Peri T Kurshan |
| author_facet | Zhao Xuan Laura Manning Jessica Nelson Janet E Richmond Daniel A Colón-Ramos Kang Shen Peri T Kurshan |
| author_sort | Zhao Xuan |
| collection | DOAJ |
| description | Active zone proteins cluster synaptic vesicles at presynaptic terminals and coordinate their release. In forward genetic screens, we isolated a novel Caenorhabditis 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 three 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. |
| first_indexed | 2024-04-12T02:08:57Z |
| format | Article |
| id | doaj.art-631e3dc98cd347b68b384be1f62e5d8d |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:08:57Z |
| publishDate | 2017-11-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-631e3dc98cd347b68b384be1f62e5d8d2022-12-22T03:52:27ZengeLife Sciences Publications LtdeLife2050-084X2017-11-01610.7554/eLife.29276Clarinet (CLA-1), a novel active zone protein required for synaptic vesicle clustering and releaseZhao Xuan0https://orcid.org/0000-0002-8254-2887Laura Manning1https://orcid.org/0000-0003-1597-0600Jessica Nelson2Janet E Richmond3Daniel A Colón-Ramos4Kang Shen5https://orcid.org/0000-0003-4059-8249Peri T Kurshan6https://orcid.org/0000-0001-6267-7103Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, United States; Department of Cell Biology, Yale University School of Medicine, New Haven, United States; Department of Neuroscience, Yale University School of Medicine, New Haven, United StatesDepartment of Biological Sciences, University of Illinois at Chicago, Chicago, IllinoisProgram in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, United States; Department of Cell Biology, Yale University School of Medicine, New Haven, United States; Department of Neuroscience, Yale University School of Medicine, New Haven, United StatesDepartment of Biological Sciences, University of Illinois at Chicago, Chicago, IllinoisProgram in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, United States; Department of Cell Biology, Yale University School of Medicine, New Haven, United States; Department of Neuroscience, Yale University School of Medicine, New Haven, United States; Instituto de Neurobiología, Recinto de Ciencias Médicas, Universidad de Puerto Rico, San Juan, Puerto RicoDepartment of Biology, Stanford University, Stanford, United States; Howard Hughes Medical InstituteDepartment of Biology, Stanford University, Stanford, United StatesActive zone proteins cluster synaptic vesicles at presynaptic terminals and coordinate their release. In forward genetic screens, we isolated a novel Caenorhabditis 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 three 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.https://elifesciences.org/articles/29276synapseactive zonepresynaptic plasticitysynaptic vesiclesynaptogenesis |
| spellingShingle | Zhao Xuan Laura Manning Jessica Nelson Janet E Richmond Daniel A Colón-Ramos Kang Shen Peri T Kurshan Clarinet (CLA-1), a novel active zone protein required for synaptic vesicle clustering and release eLife synapse active zone presynaptic plasticity synaptic vesicle synaptogenesis |
| title | Clarinet (CLA-1), a novel active zone protein required for synaptic vesicle clustering and release |
| title_full | Clarinet (CLA-1), a novel active zone protein required for synaptic vesicle clustering and release |
| title_fullStr | Clarinet (CLA-1), a novel active zone protein required for synaptic vesicle clustering and release |
| title_full_unstemmed | Clarinet (CLA-1), a novel active zone protein required for synaptic vesicle clustering and release |
| title_short | Clarinet (CLA-1), a novel active zone protein required for synaptic vesicle clustering and release |
| title_sort | clarinet cla 1 a novel active zone protein required for synaptic vesicle clustering and release |
| topic | synapse active zone presynaptic plasticity synaptic vesicle synaptogenesis |
| url | https://elifesciences.org/articles/29276 |
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