title: Systematic analysis of genes required for synapse structure and function.
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.
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
authors.forename: Derek
authors.initials: D
authors.lastname: Sieburth
authors.forename: QueeLim
authors.initials: Q
authors.lastname: Ch'ng
authors.forename: Michael
authors.initials: M
authors.lastname: Dybbs
authors.forename: Masoud
authors.initials: M
authors.lastname: Tavazoie
authors.forename: Scott
authors.initials: S
authors.lastname: Kennedy
authors.forename: Duo
authors.initials: D
authors.lastname: Wang
authors.forename: Denis
authors.initials: D
authors.lastname: Dupuy
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Rual
authors.forename: David E
authors.initials: DE
authors.lastname: Hill
authors.forename: Marc
authors.initials: M
authors.lastname: Vidal
authors.forename: Gary
authors.initials: G
authors.lastname: Ruvkun
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Kaplan
mesh_terms: D000448:Aldicarb / Q000494:pharmacology; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D016000:Cluster Analysis; D003599:Cytoskeleton / Q000378:metabolism; D004351:Drug Resistance / Q000235:genetics; D005453:Fluorescence; D020869:Gene Expression Profiling; D008565:Membrane Proteins / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism; D009046:Motor Neurons / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009469:Neuromuscular Junction / Q000166:cytology / Q000235:genetics / Q000502:physiology; D009479:Neuropeptides / Q000378:metabolism; D010703:Phorbol Esters / Q000494:pharmacology; D021381:Protein Transport; D050683:R-SNARE Proteins; D034622:RNA Interference; D013569:Synapses / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D009435:Synaptic Transmission / Q000235:genetics*; D013572:Synaptic Vesicles / Q000378:metabolism; D000099273:Neurabins
chemical_list: D000448:Aldicarb; D029742:Caenorhabditis elegans Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D010703:Phorbol Esters; D050683:R-SNARE Proteins; D000099273:Neurabins