Department of Neurobiology; Francis Lab; Graduate School of Biomedical Sciences, Neuroscience Program
Medical Subject Headings
Amino Acid Substitution; Animals; Behavior, Animal; Caenorhabditis elegans; Calnexin; Calreticulin; Cell Death; Genes, Reporter; Homeostasis; Ion Channels; Locomotion; Microscopy, Confocal; Motor Neuron Disease; Necrosis; Nerve Degeneration; Paralysis; Receptors, Nicotinic; Signal Transduction
Neuroscience and Neurobiology
Inappropriate or excessive activation of ionotropic receptors can have dramatic consequences for neuronal function and, in many instances, leads to cell death. In Caenorhabditis elegans, nicotinic acetylcholine receptor (nAChR) subunits are highly expressed in a neural circuit that controls movement. Here, we show that heteromeric nAChRs containing the acr-2 subunit are diffusely localized in the processes of excitatory motor neurons and act to modulate motor neuron activity. Excessive signaling through these receptors leads to cell-autonomous degeneration of cholinergic motor neurons and paralysis. C. elegans double mutants lacking calreticulin and calnexin-two genes previously implicated in the cellular events leading to necrotic-like cell death (Xu et al. 2001)-are resistant to nAChR-mediated toxicity and possess normal numbers of motor neuron cell bodies. Nonetheless, excess nAChR activation leads to progressive destabilization of the motor neuron processes and, ultimately, paralysis in these animals. Our results provide new evidence that chronic activation of ionotropic receptors can have devastating degenerative effects in neurons and reveal that ion channel-mediated toxicity may have distinct consequences in neuronal cell bodies and processes.
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Citation: Barbagallo B, Prescott HA, Boyle P, Climer J, Francis, MM. (2010) A Dominant Mutation in a Neuronal Acetylcholine Receptor Subunit Leads to Motor Neuron Degeneration in Caenorhabditis elegans The Journal of Neuroscience, 30(42):13932-13942; doi:10.1523/JNEUROSCI.1515-10.2010. Link to article on publisher's website
Copyright © 2010 the authors. This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported License, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/.
The Journal of neuroscience : the official journal of the Society for Neuroscience
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Barbagallo, Belinda; Prescott, Hilary A.; Boyle, Patrick; Climer, Jason; and Francis, Michael M., "A dominant mutation in a neuronal acetylcholine receptor subunit leads to motor neuron degeneration in Caenorhabditis elegans" (2010). GSBS Student Publications. 1679.