RRC ID 429
Author Kim H, Rogers MJ, Richmond JE, McIntire SL.
Title SNF-6 is an acetylcholine transporter interacting with the dystrophin complex in Caenorhabditis elegans.
Journal Nature
Abstract Muscular dystrophies are among the most common human genetic diseases and are characterized by progressive muscle degeneration. Muscular dystrophies result from genetic defects in components of the dystrophin-glycoprotein complex (DGC), a multimeric complex found in the muscle cell plasma membrane. The DGC links the intracellular cytoskeleton to the extracellular matrix and is thought to be important for maintaining the mechanical integrity of muscles and organizing signalling molecules. The exact role of the DGC in the pathogenesis of disease has, however, remained uncertain. Mutations in Caenorhabditis elegans DGC genes lead to specific defects in coordinated movement and can also cause muscle degeneration. Here we show that mutations in the gene snf-6 result in phenotypes indistinguishable from those of the DGC mutants, and that snf-6 encodes a novel acetylcholine/choline transporter. SNF-6 mediates the uptake of acetylcholine at neuromuscular junctions during periods of increased synaptic activity. SNF-6 also interacts with the DGC, and mutations in DGC genes cause a loss of SNF-6 at neuromuscular junctions. Improper clearing of acetylcholine and prolonged excitation of muscles might contribute to the pathogenesis of muscular dystrophies.
Volume 430(7002)
Pages 891-6
Published 2004-8-19
DOI 10.1038/nature02798
PII nature02798
PMID 15318222
MeSH Amino Acid Sequence Animals Biological Transport Blotting, Western Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / chemistry Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Dystrophin / chemistry* Dystrophin / metabolism* Electrophysiology Macromolecular Substances Molecular Sequence Data Muscles / metabolism Muscles / physiology Mutation / genetics Phenotype Precipitin Tests Protein Binding Sodium / pharmacology Symporters / chemistry Symporters / genetics Symporters / metabolism* Synapses / metabolism
IF 42.779
Times Cited 36
C.elegans tm373