Acetylcholinesterase function is dispensable for sensory neurite growth but is critical for neuromuscular synapse stability. 2004

Gerald B Downes, and Michael Granato
Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6058, USA.

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.

UI MeSH Term Description Entries
D009043 Motor Activity Body movements of a human or an animal as a behavioral phenomenon. Activities, Motor,Activity, Motor,Motor Activities
D009469 Neuromuscular Junction The synapse between a neuron and a muscle. Myoneural Junction,Nerve-Muscle Preparation,Junction, Myoneural,Junction, Neuromuscular,Junctions, Myoneural,Junctions, Neuromuscular,Myoneural Junctions,Nerve Muscle Preparation,Nerve-Muscle Preparations,Neuromuscular Junctions,Preparation, Nerve-Muscle,Preparations, Nerve-Muscle
D009475 Neurons, Afferent Neurons which conduct NERVE IMPULSES to the CENTRAL NERVOUS SYSTEM. Afferent Neurons,Afferent Neuron,Neuron, Afferent
D011950 Receptors, Cholinergic Cell surface proteins that bind acetylcholine with high affinity and trigger intracellular changes influencing the behavior of cells. Cholinergic receptors are divided into two major classes, muscarinic and nicotinic, based originally on their affinity for nicotine and muscarine. Each group is further subdivided based on pharmacology, location, mode of action, and/or molecular biology. ACh Receptor,Acetylcholine Receptor,Acetylcholine Receptors,Cholinergic Receptor,Cholinergic Receptors,Cholinoceptive Sites,Cholinoceptor,Cholinoceptors,Receptors, Acetylcholine,ACh Receptors,Receptors, ACh,Receptor, ACh,Receptor, Acetylcholine,Receptor, Cholinergic,Sites, Cholinoceptive
D002038 Bungarotoxins Neurotoxic proteins from the venom of the banded or Formosan krait (Bungarus multicinctus, an elapid snake). alpha-Bungarotoxin blocks nicotinic acetylcholine receptors and has been used to isolate and study them; beta- and gamma-bungarotoxins act presynaptically causing acetylcholine release and depletion. Both alpha and beta forms have been characterized, the alpha being similar to the large, long or Type II neurotoxins from other elapid venoms. alpha-Bungarotoxin,beta-Bungarotoxin,kappa-Bungarotoxin,alpha Bungarotoxin,beta Bungarotoxin,kappa Bungarotoxin
D002217 Carbachol A slowly hydrolyzed CHOLINERGIC AGONIST that acts at both MUSCARINIC RECEPTORS and NICOTINIC RECEPTORS. Carbamylcholine,Carbacholine,Carbamann,Carbamoylcholine,Carbastat,Carbocholine,Carboptic,Doryl,Isopto Carbachol,Jestryl,Miostat,Carbachol, Isopto
D004625 Embryo, Nonmammalian The developmental entity of a fertilized egg (ZYGOTE) in animal species other than MAMMALS. For chickens, use CHICK EMBRYO. Embryonic Structures, Nonmammalian,Embryo, Non-Mammalian,Embryonic Structures, Non-Mammalian,Nonmammalian Embryo,Nonmammalian Embryo Structures,Nonmammalian Embryonic Structures,Embryo Structure, Nonmammalian,Embryo Structures, Nonmammalian,Embryo, Non Mammalian,Embryonic Structure, Non-Mammalian,Embryonic Structure, Nonmammalian,Embryonic Structures, Non Mammalian,Embryos, Non-Mammalian,Embryos, Nonmammalian,Non-Mammalian Embryo,Non-Mammalian Embryonic Structure,Non-Mammalian Embryonic Structures,Non-Mammalian Embryos,Nonmammalian Embryo Structure,Nonmammalian Embryonic Structure,Nonmammalian Embryos,Structure, Non-Mammalian Embryonic,Structure, Nonmammalian Embryo,Structure, Nonmammalian Embryonic,Structures, Non-Mammalian Embryonic,Structures, Nonmammalian Embryo,Structures, Nonmammalian Embryonic
D000109 Acetylcholine A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. 2-(Acetyloxy)-N,N,N-trimethylethanaminium,Acetilcolina Cusi,Acetylcholine Bromide,Acetylcholine Chloride,Acetylcholine Fluoride,Acetylcholine Hydroxide,Acetylcholine Iodide,Acetylcholine L-Tartrate,Acetylcholine Perchlorate,Acetylcholine Picrate,Acetylcholine Picrate (1:1),Acetylcholine Sulfate (1:1),Bromoacetylcholine,Chloroacetylcholine,Miochol,Acetylcholine L Tartrate,Bromide, Acetylcholine,Cusi, Acetilcolina,Fluoride, Acetylcholine,Hydroxide, Acetylcholine,Iodide, Acetylcholine,L-Tartrate, Acetylcholine,Perchlorate, Acetylcholine
D000110 Acetylcholinesterase An enzyme that catalyzes the hydrolysis of ACETYLCHOLINE to CHOLINE and acetate. In the CNS, this enzyme plays a role in the function of peripheral neuromuscular junctions. EC 3.1.1.7. Acetylcholine Hydrolase,Acetylthiocholinesterase,Hydrolase, Acetylcholine
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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