Systematic analysis of genes required for synapse structure and function

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 and Joshua M. Kaplan ()
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Derek Sieburth: Massachusetts General Hospital
QueeLim Ch'ng: Massachusetts General Hospital
Michael Dybbs: Massachusetts General Hospital
Masoud Tavazoie: Massachusetts General Hospital
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
Gary Ruvkun: Massachusetts General Hospital
Joshua M. Kaplan: Massachusetts General Hospital

Nature, 2005, vol. 436, issue 7050, 510-517

Abstract: 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.

Date: 2005
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DOI: 10.1038/nature03809

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