Additional genes which result in an elevation of acetylcholine levels by mutations in Caenorhabditis elegans

Hosono, Ryuji; Kamiya, Yushi

doi:10.1016/0304-3940(91)90270-4

Cited by 47 publications

(39 citation statements)

References 9 publications

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“…mutants is a commonly used indicator of neuromuscular signaling defects and in the past has revealed a multitude of components required for efficient neurotransmission (Brenner, 1974;Hosono and Kamiya, 1991;Miller et al, 1996). Third, the motor axon defects as well as locomotory defects worsen significantly during the life of an animal.…”

Section: Discussionmentioning

confidence: 99%

“…We tested more directly whether unc-122 mutants display defects in synaptic signaling by using two neuroactive drugs, aldicarb and levamisole, that are used to dissect neuromuscular signaling in C. elegans (Brenner, 1974;Hosono and Kamiya, 1991;Miller et al, 1996). Aldicarb inhibits acetyl cholinesterase (AChE), causing an accumulation of acetylcholine at the neuromuscular junction (NMJ), overstimulation of acetylcholine receptors, and eventual paralysis of wild-type animals.…”

Section: Unc-122 Mutants Display a Defective Sensitivity To Cholinergmentioning

confidence: 99%

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A Conserved Postsynaptic Transmembrane Protein Affecting Neuromuscular Signaling inCaenorhabditis elegans

Loria¹,

Hodgkin²,

Hobert³

2004

J. Neurosci.

116

109

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For a motor unit to function, neurons and muscle cells need to adopt their correct cell fate, form appropriate cellular contacts, and assemble a specific repertoire of signaling proteins into presynaptic and postsynaptic structures. In the nematode Caenorhabditis elegans, a disruption of any of these steps causes uncoordinated locomotory behavior (unc phenotype). We report here the positional cloning of a new unc gene, unc-122, which we show by mosaic analysis and tissue-specific rescue experiments to act in muscle to affect locomotory behavior. unc-122 codes for a phylogenetically conserved type II transmembrane protein with collagen repeats and a cysteine-rich olfactomedin domain. Together with uncharacterized proteins in C. elegans, Drosophila, and vertebrates, UNC-122 defines a novel family of proteins that we term "Colmedins." UNC-122 protein is expressed exclusively in muscle and coelomocytes and localizes to the postsynaptic surface of GABAergic and cholinergic neuromuscular junctions (NMJs). Presynaptic and postsynaptic structures are present and properly aligned in unc-122 mutant animals, yet the animals display neurotransmission defects characterized by an altered sensitivity toward drugs that interfere with cholinergic signaling. Moreover, unc-122 mutant animals display anatomical defects in motor axons that are likely a secondary consequence of neurotransmission defects. Both the neuroanatomical and locomotory defects worsen progressively during the life of an animal, consistent with a role of unc-122 in acute signaling at the NMJ. On the basis of motifs in the UNC-122 protein sequence that are characteristic of extracellular matrix proteins, we propose that UNC-122 is involved in maintaining a structural microenvironment that allows efficient neuromuscular signaling.

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Section: Discussionmentioning

confidence: 99%

Section: Unc-122 Mutants Display a Defective Sensitivity To Cholinergmentioning

confidence: 99%

A Conserved Postsynaptic Transmembrane Protein Affecting Neuromuscular Signaling inCaenorhabditis elegans

Loria¹,

Hodgkin²,

Hobert³

2004

J. Neurosci.

116

109

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“…In C. elegans, resistance to aldicarb is well correlated with synaptic defects (reviewed by Rand and Nonet, 1997). The unc-11 gene is thought to function presynaptically because acetylcholine levels are elevated in the mutant (Hosono and Kamiya, 1991;Nguyen et al, 1995) and because the animals respond normally to acetylcholine receptor agonists (Miller et al, 1996). In addition to a defect in cholinergic transmission, unc-11 mutants have a defect in ␥-aminobutyric acid (GABA)-ergic transmission.…”

Section: Unc-11 Function Is Required By Multiplementioning

confidence: 99%

UNC-11, aCaenorhabditis elegansAP180 Homologue, Regulates the Size and Protein Composition of Synaptic Vesicles

Nonet

Holgado

Brewer

et al. 1999

MBoC

249

207

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The unc-11 gene of Caenorhabditis elegans encodes multiple isoforms of a protein homologous to the mammalian brain-specific clathrin-adaptor protein AP180. The UNC-11 protein is expressed at high levels in the nervous system and at lower levels in other tissues. In neurons, UNC-11 is enriched at presynaptic terminals but is also present in cell bodies. unc-11mutants are defective in two aspects of synaptic vesicle biogenesis. First, the SNARE protein synaptobrevin is mislocalized, no longer being exclusively localized to synaptic vesicles. The reduction of synaptobrevin at synaptic vesicles is the probable cause of the reduced neurotransmitter release observed in these mutants. Second,unc-11 mutants accumulate large vesicles at synapses. We propose that the UNC-11 protein mediates two functions during synaptic vesicle biogenesis: it recruits synaptobrevin to synaptic vesicle membranes and it regulates the size of the budded vesicle during clathrin coat assembly.

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“…We also examined the levels of the neurotransmitter acetylcholine in the rab mutants, because other mutants lacking synaptic components accumulate this transmitter (Hosono et al, 1987;Hosono and Kamiya, 1991;Nonet et al, 1993;Nguyen, 1995). However, acetylcholine levels were normal in rab-3 mutants (Table 1).…”

Section: -C Lateral View Of the Head Region Of A Rab-3( Js49) Adult mentioning

confidence: 99%

Caenorhabditis elegans rab-3Mutant Synapses Exhibit Impaired Function and Are Partially Depleted of Vesicles

et al. 1997

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Rab molecules regulate vesicular trafficking in many different exocytic and endocytic transport pathways in eukaryotic cells. In neurons, rab3 has been proposed to play a crucial role in regulating synaptic vesicle release. To elucidate the role of rab3 in synaptic transmission, we isolated and characterized Caenorhabditis elegans rab-3 mutants. Similar to the mouse rab3A mutants, these mutants survived and exhibited only mild behavioral abnormalities. In contrast to the mouse mutants, synaptic transmission was perturbed in these animals. Extracellular electrophysiological recordings revealed that synaptic transmission in the pharyngeal nervous system was impaired. Furthermore, rab-3 animals were resistant to the acetylcholinesterase inhibitor aldicarb, suggesting that cholinergic transmission was generally depressed. Last, synaptic vesicle populations were redistributed in rab-3 mutants. In motor neurons, vesicle populations at synapses were depleted to 40% of normal levels, whereas in intersynaptic regions of the axon, vesicle populations were elevated. On the basis of the morphological defects at neuromuscular junctions, we postulate that RAB-3 may regulate recruitment of vesicles to the active zone or sequestration of vesicles near release sites.

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Additional genes which result in an elevation of acetylcholine levels by mutations in Caenorhabditis elegans

Cited by 47 publications

References 9 publications

A Conserved Postsynaptic Transmembrane Protein Affecting Neuromuscular Signaling inCaenorhabditis elegans

A Conserved Postsynaptic Transmembrane Protein Affecting Neuromuscular Signaling inCaenorhabditis elegans

UNC-11, aCaenorhabditis elegansAP180 Homologue, Regulates the Size and Protein Composition of Synaptic Vesicles

Caenorhabditis elegans rab-3Mutant Synapses Exhibit Impaired Function and Are Partially Depleted of Vesicles

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