title: The Cell Death Pathway Regulates Synapse Elimination through Cleavage of Gelsolin in Caenorhabditis elegans Neurons.
abstract: Synapse elimination occurs in development, plasticity, and disease. Although the importance of synapse elimination has been documented in many studies, the molecular mechanisms underlying this process are unclear. Here, using the development of C. elegans RME neurons as a model, we have uncovered a function for the apoptosis pathway in synapse elimination. We find that the conserved apoptotic cell death (CED) pathway and axonal mitochondria are required for the elimination of transiently formed clusters of presynaptic components in RME neurons. This function of the CED pathway involves the activation of the actin-filament-severing protein, GSNL-1. Furthermore, we show that caspase CED-3 cleaves GSNL-1 at a conserved C-terminal region and that the cleaved active form of GSNL-1 promotes its actin-severing ability. Our data suggest that activation of the CED pathway contributes to selective elimination of synapses through disassembly of the actin filament network.
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Research Drive, Durham, NC 27710, USA.
authors.forename: Lingfeng
authors.initials: L
authors.lastname: Meng
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Toronto, ON M5G 1X5, Canada.
authors.forename: Ben
authors.initials: B
authors.lastname: Mulcahy
authors.affiliation: Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Cook
authors.affiliation: Department of Physics and Center for Brain Science, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Marianna
authors.initials: M
authors.lastname: Neubauer
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Research Drive, Durham, NC 27710, USA.
authors.forename: Airong
authors.initials: A
authors.lastname: Wan
authors.affiliation: Neurobiology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA; Department of Cellular and Molecular Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
authors.forename: Yishi
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Research Drive, Durham, NC 27710, USA; Department of Neurobiology and Duke Institute for Brain Sciences, Duke University Medical Center, Research Drive, Durham, NC 27710, USA. Electronic address: dong.yan@duke.edu.
authors.forename: Dong
authors.initials: D
authors.lastname: Yan
mesh_terms: D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D052139:Intracellular Calcium-Sensing Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D059748:Proteolysis; D013569:Synapses / Q000378:metabolism* / Q000473:pathology
chemical_list: D000199:Actins; D029742:Caenorhabditis elegans Proteins; C532447:GSNL-1 protein, C elegans; D052139:Intracellular Calcium-Sensing Proteins; D020169:Caspases; C089223:ced-3 protein, C elegans