@article{434a533715f74402a254fd353fbf7eb7,
title = "Clarinet (CLA-1), a novel active zone protein required for synaptic vesicle clustering and release",
abstract = "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.",
author = "Zhao Xuan and Laura Manning and Jessica Nelson and Richmond, {Janet E.} and Col{\'o}n-Ramos, {Daniel A.} and Kang Shen and Kurshan, {Peri T.}",
note = "Funding Information: We thank Reiner Bleher for technical assistance with the electron microscopy, Pengpeng Li for assistance constructing the phylogenic tree, Lewie Zeng and Marc Hammarlund for assistance with CRISPR protocols, SoRi Jang, Gabriela Bosque, Lucelenie Rodriguez, Katie Underwood, Gonzalo Tueros and Nathan Cook for help in identifying and characterizing the cla-1 allele from the forward genetic screens. We would like to thank Jim Rand for discussions of unpublished data. We thank Cori Bargmann, Yishi Jin and Jihong Bai and the Caenorhabditis Genetics Center (supported by the National Institutes of Health Office of Research Infrastructure Programs; P40 OD010440) for strains. We thank the Research Center for Minority Institutions program and the Instituto de Neurobiolog{\'i}a de la Universidad de Puerto Rico for providing a meeting and brainstorming platforms. DAC-R, ZX and JN were supported by NIH (R01NS076558) and the National Science Foundation (NSF IOS 1353845). PTK and KS were supported by NIH (5R01NS048392) and the Howard Hughes Medical Institute. This work made use of the EPIC facility (NUANCE Center-Northwestern University), which has received support from the MRSEC program (NSF DMR-1121262) at the Materials Research Center; the International Institute for Nanotechnology (IIN); and the State of Illinois, through the IIN. Funding Information: National Science Foundation Publisher Copyright: {\textcopyright} Xuan et al.",
year = "2017",
month = nov,
day = "21",
doi = "10.7554/eLife.29276",
language = "English (US)",
volume = "6",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
}