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Systematic analysis of genes required for synapse structure and function

Author

Listed:
  • Derek Sieburth

    (Massachusetts General Hospital)

  • QueeLim Ch'ng

    (Massachusetts General Hospital)

  • Michael Dybbs

    (Massachusetts General Hospital)

  • Masoud Tavazoie

    (Massachusetts General Hospital
    Columbia University)

  • Scott Kennedy

    (University of Wisconsin)

  • Duo Wang

    (Massachusetts General Hospital)

  • Denis Dupuy

    (Dana-Farber Cancer Institute)

  • Jean-François Rual

    (Dana-Farber Cancer Institute)

  • David E. Hill

    (Dana-Farber Cancer Institute)

  • Marc Vidal

    (Dana-Farber Cancer Institute
    Harvard Medical School)

  • Gary Ruvkun

    (Massachusetts General Hospital
    Harvard Medical School)

  • Joshua M. Kaplan

    (Massachusetts General Hospital
    Harvard Medical School)

Abstract

Chemical synapses are complex structures that mediate rapid intercellular signalling in the nervous system. Proteomic studies suggest that several hundred proteins will be found at synaptic specializations. Here we describe a systematic screen to identify genes required for the function or development of Caenorhabditis elegans neuromuscular junctions. A total of 185 genes were identified in an RNA interference screen for decreased acetylcholine secretion; 132 of these genes had not previously been implicated in synaptic transmission. Functional profiles for these genes were determined by comparing secretion defects observed after RNA interference under a variety of conditions. Hierarchical clustering identified groups of functionally related genes, including those involved in the synaptic vesicle cycle, neuropeptide signalling and responsiveness to phorbol esters. Twenty-four genes encoded proteins that were localized to presynaptic specializations. Loss-of-function mutations in 12 genes caused defects in presynaptic structure.

Suggested Citation

  • Derek Sieburth & QueeLim Ch'ng & Michael Dybbs & Masoud Tavazoie & Scott Kennedy & Duo Wang & Denis Dupuy & Jean-François Rual & David E. Hill & Marc Vidal & Gary Ruvkun & Joshua M. Kaplan, 2005. "Systematic analysis of genes required for synapse structure and function," Nature, Nature, vol. 436(7050), pages 510-517, July.
    • Handle: RePEc:nat:nature:v:436:y:2005:i:7050:d:10.1038_nature03809
    DOI: 10.1038/nature03809
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    Cited by:

    1. Alon Kaufman & Gideon Dror & Isaac Meilijson & Eytan Ruppin, 2006. "Gene Expression of Caenorhabditis elegans Neurons Carries Information on Their Synaptic Connectivity," PLOS Computational Biology, Public Library of Science, vol. 2(12), pages 1-7, December.
    2. Maria E Gallegos & Sanjeev Balakrishnan & Priya Chandramouli & Shaily Arora & Aruna Azameera & Anitha Babushekar & Emilee Bargoma & Abdulmalik Bokhari & Siva Kumari Chava & Pranti Das & Meetali Desai , 2012. "The C. elegans Rab Family: Identification, Classification and Toolkit Construction," PLOS ONE, Public Library of Science, vol. 7(11), pages 1-19, November.
    3. Sabrina Villar-Pazos & Laurel Thomas & Yunhan Yang & Kun Chen & Jenea B. Lyles & Bradley J. Deitch & Joseph Ochaba & Karen Ling & Berit Powers & Sebastien Gingras & Holly B. Kordasiewicz & Melanie J. , 2023. "Neural deficits in a mouse model of PACS1 syndrome are corrected with PACS1- or HDAC6-targeting therapy," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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