RRC ID 3399
Author Sieburth D, Ch'ng Q, Dybbs M, Tavazoie M, Kennedy S, Wang D, Dupuy D, Rual JF, Hill DE, Vidal M, Ruvkun G, Kaplan JM.
Title Systematic analysis of genes required for synapse structure and function.
Journal Nature
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.
Volume 436(7050)
Pages 510-7
Published 2005-7-28
DOI 10.1038/nature03809
PII nature03809
PMID 16049479
MeSH Aldicarb / pharmacology Animals Caenorhabditis elegans / genetics* Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics* Cluster Analysis Cytoskeleton / metabolism Drug Resistance / genetics Fluorescence Gene Expression Profiling Membrane Proteins / metabolism Microfilament Proteins / metabolism Motor Neurons / metabolism Mutation / genetics Nerve Tissue Proteins / metabolism Neuromuscular Junction / cytology Neuromuscular Junction / genetics Neuromuscular Junction / physiology Neuropeptides / metabolism Phorbol Esters / pharmacology Protein Transport R-SNARE Proteins RNA Interference Synapses / chemistry Synapses / genetics* Synapses / physiology* Synaptic Transmission / genetics* Synaptic Vesicles / metabolism
IF 42.779
Times Cited 262
WOS Category NEUROSCIENCES
Resource
C.elegans tm292