Genetic defects in acetylcholine signalling promote protein degradation in muscle cells of Caenorhabditis elegans.
A myosin-lacZ fusion, expressed in 103 muscle cells of Caenorhabditis elegans, reports on how proteolysis in muscle is controlled by neural and intramuscular signals. Upon acute starvation, the fusion protein is degraded in the posterior 63 cells of the body-wall muscle, but remains stable in 32 anterior body-wall muscles and 8 vulval muscle cells. This distinction correlates with differences in the innervation of these cells. Reporter protein in the head and vulval muscles becomes labile upon genetic 'denervation' in mutants that have blocks in pre-synaptic synthesis or release of acetylcholine (ACh) or post-synaptic reception at nicotinic ACh receptors (nAChR), whereas protein in all 103 muscles is stabilized by the nicotinic agonist levamisole in the absence of ACh production. Levamisole does not stabilize muscle protein in nAChR mutants that are behaviorally resistant to levamisole. Neural inputs thus exert negative control over the proteolytic process in muscle by stimulating muscle nicotinic ACh receptors.
Szewczyk
N J
NJ
Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Hartman
J J
JJ
Barmada
S J
SJ
Jacobson
L A
LA
D000109:Acetylcholine / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D001284:Atrophy; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000502:physiology; D009097:Multienzyme Complexes / Q000502:physiology; D009121:Muscle Denervation; D018485:Muscle Fibers, Skeletal / Q000378:metabolism* / Q000473:pathology; D009124:Muscle Proteins / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D011978:Receptors, Nicotinic / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics*; D014452:Ubiquitins / Q000378:metabolism
D009097:Multienzyme Complexes; D009124:Muscle Proteins; D011978:Receptors, Nicotinic; D014452:Ubiquitins; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D000109:Acetylcholine