Acetylcholinesterase function is dispensable for sensory neurite growth but is critical for neuromuscular synapse stability.
The enzyme acetylcholinesterase (AChE) terminates synaptic transmission at cholinergic synapses by hydrolyzing the neurotransmitter acetylcholine. In addition, AChE is thought to play several 'non-classical' roles that do not require catalytic function. Most prominent among these is facilitation of neurite growth. Here, we report that the zebrafish zieharmonika (zim) locus encodes AChE. We show that one mutant zim allele is caused by a pre-mature stop codon, resulting in a truncated protein that lacks both the catalytic site and the carboxy-terminal neuritogenic domain. To explore the 'non-classical' role of AChE, we examined embryos mutant for this allele. In contrast to previous results using a catalytic-inactive allele, our analysis demonstrates that AChE is dispensable for muscle fiber development and Rohon-Beard sensory neuron growth and survival. Moreover, we show that in the absence of AChE, acetylcholine receptor clusters at neuromuscular junctions initially assemble, but that these clusters are not maintained. Taken together, our results demonstrate that AChE is dispensable for its proposed non-classical roles in muscle fiber formation and sensory neuron development, but is crucial for regulating the stability of neuromuscular synapses.
Downes
Gerald B
GB
Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6058, USA.
Granato
Michael
M
D000109:Acetylcholine / Q000378:metabolism; D000110:Acetylcholinesterase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002038:Bungarotoxins / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D020134:Catalytic Domain; D016923:Cell Death; D018679:Cholinergic Agonists / Q000494:pharmacology; D018388:Codon, Terminator; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D020287:In Situ Nick-End Labeling; D009043:Motor Activity; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000502:physiology; D009469:Neuromuscular Junction / Q000502:physiology*; D009475:Neurons, Afferent / Q000166:cytology* / Q000201:enzymology* / Q000502:physiology; D011950:Receptors, Cholinergic / Q000378:metabolism; D015027:Zebrafish / Q000033:anatomy & histology / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
D002038:Bungarotoxins; D018679:Cholinergic Agonists; D018388:Codon, Terminator; D011950:Receptors, Cholinergic; D029961:Zebrafish Proteins; D002217:Carbachol; D000110:Acetylcholinesterase; D000109:Acetylcholine