Molecular, genetic and physiological characterisation of dystrobrevin-like (dyb-1) mutants of Caenorhabditis elegans.
Dystrobrevins are protein components of the dystrophin complex, whose disruption leads to Duchenne muscular dystrophy and related diseases. The Caenorhabditis elegans dystrobrevin gene (dyb-1) encodes a protein 38 % identical with its mammalian counterparts. The C. elegans dystrobrevin is expressed in muscles and neurons. We characterised C. elegans dyb-1 mutants and showed that: (1) their behavioural phenotype resembles that of dystrophin (dys-1) mutants; (2) the phenotype of dyb-1 dys-1 double mutants is not different from the single ones; (3) dyb-1 mutants are more sensitive than wild-type animals to reductions of acetylcholinesterase levels and have an increased response to acetylcholine; (4) dyb-1 mutations alone do not lead to muscle degeneration, but synergistically produce a progressive myopathy when combined with a mild MyoD/hlh-1 mutation. All together, these findings further substantiate the role of dystrobrevins in cholinergic transmission and as functional partners of dystrophin.
CGMC, CNRS-UMR 5534, Université Lyon1, 43 bld du 11 Novembre, 69622 Villeurbanne cedex, France.
K
K
Gieseler
M C
MC
Mariol
C
C
Bessou
M
M
Migaud
C J
CJ
Franks
L
L
Holden-Dye
L
L
Ségalat
D000109:Acetylcholine / Q000502:physiology; D000110:Acetylcholinesterase / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000502:physiology; D029742:Caenorhabditis elegans Proteins; D003001:Cloning, Molecular; D004195:Disease Models, Animal; D004594:Electrophysiology; D005452:Fluoresceins; D015870:Gene Expression; D015801:Helminth Proteins / Q000235:genetics* / Q000502:physiology; D008969:Molecular Sequence Data; D009124:Muscle Proteins; D009135:Muscular Diseases / Q000235:genetics / Q000503:physiopathology; D009154:Mutation; D018006:Myogenic Regulatory Factors; D009419:Nerve Tissue Proteins; D009479:Neuropeptides / Q000235:genetics* / Q000502:physiology; D009687:Nuclear Proteins; D010042:Ouabain / Q000031:analogs & derivatives; D010641:Phenotype; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology
D029742:Caenorhabditis elegans Proteins; C479075:Dyb-1 protein, C elegans; D005452:Fluoresceins; D015801:Helminth Proteins; D009124:Muscle Proteins; D018006:Myogenic Regulatory Factors; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D009687:Nuclear Proteins; D014157:Transcription Factors; C109049:rhodol green-ethylenediamine-ouabain; C066645:HLH-1 protein, C elegans; D010042:Ouabain; D000110:Acetylcholinesterase; D000109:Acetylcholine