Systematic analysis of genes required for synapse structure and function.

Full 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.

Author information

Author/s: Sieburth, Derek (D); 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);

Affiliation: Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.

Journal: Nature (Nature), published in England. (Language: eng)

Reference: 2005-Jul; vol 436 (issue 7050) : pp 510-7

Dates: Created 2005/07/28; Completed 2005/08/10; Revised 2006/11/15;

PMID: 16049479, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

Comments and Corrections

CommentIn: Nature. 2005 Jul 28;436(7050):473-4. (PMID: 16049464)

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Aldicarb - pharmacology
Animals
Caenorhabditis elegans - genetics; 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

Motor Neurons - metabolism
Mutation - genetics
Nerve Tissue Proteins - metabolism
Neuromuscular Junction - cytology; genetics; physiology
Neuropeptides - metabolism; secretion
Phorbol Esters - pharmacology
Protein Transport
R-SNARE Proteins
RNA Interference
Synapses - chemistry; genetics; physiology
Synaptic Transmission - genetics
Synaptic Vesicles - metabolism

Associated Chemicals: Caenorhabditis elegans Proteins (0) ; Membrane Proteins (0) ; Microfilament Proteins (0) ; Nerve Tissue Proteins (0) ; Neuropeptides (0) ; Phorbol Esters (0) ; R-SNARE Proteins (0) ; neurabin (0) ; Aldicarb (116-06-3)

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