Systematic analysis of genes required for synapse structure and function.
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.
Sieburth
Derek
D
Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Ch'ng
QueeLim
Q
Dybbs
Michael
M
Tavazoie
Masoud
M
Kennedy
Scott
S
Wang
Duo
D
Dupuy
Denis
D
Rual
Jean-François
JF
Hill
David E
DE
Vidal
Marc
M
Ruvkun
Gary
G
Kaplan
Joshua M
JM
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
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