Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.7 (acetylcholinesterase)
 28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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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PMID:Caenorhabditis elegans rab-3 mutant synapses exhibit impaired function and are partially depleted of vesicles. 933 82

The control of vesicle-mediated transport in nerve cells is of great importance in the function, development and maintenance of synapse. In this paper, we characterize the new Caenorhabditis elegans gene, lnp-1. The lnp-1 gene is broadly distributed in many neuronal structures and its localization is dependent of the UNC-104/kinesin protein. Deletion mutations in lnp-1 result in increased resistance to aldicarb, an acetylcholinesterase inhibitor, and in locomotor defects. However, sensitivity to levamisole, a nicotinic agonist which, unlike aldicarb, only affects postsynaptic function, was similar to that of wild-type animals, suggesting a presynaptic function for LNP-1 in neurotransmission. The mislocalization of presynaptic proteins, such as synaptobrevin-1 or RAB-3, in lnp-1 mutants further supports this hypothesis. In summary, our studies suggest that LNP-1 plays a role in synaptogenesis by regulating vesicular transport or localization.
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PMID:The evolutionarily conserved gene LNP-1 is required for synaptic vesicle trafficking and synaptic transmission. 1827 15

Microtubule plus-end directed trafficking is dominated by kinesin motors, yet kinesins differ in terms of cargo identity, movement rate, and distance travelled. Functional diversity of kinesins is especially apparent in polarized neurons, where long distance trafficking is required for efficient signal transduction-behavioral response paradigms. The Kinesin-3 superfamily are expressed in neurons and are hypothesized to have significant roles in neuronal signal transduction due to their high processivity. Although much is known about Kinesin-3 motors mechanistically in vitro, there is little known about their mechanisms in vivo. Here, we analyzed KLP-4, the Caenorhabditis elegans homologue of human KIF13A and KIF13B. Like other Kinesin-3 superfamily motors, klp-4 is highly expressed in the ventral nerve cord command interneurons of the animal, suggesting it might have a role in controlling movement of the animal. We characterized an allele of klp-4 that contains are large indel in the cargo binding domain of the motor, however, the gene still appears to be expressed. Behavioral analysis demonstrated that klp-4 mutants have defects in locomotive signaling, but not the strikingly uncoordinated movements such as those found in unc-104/KIF1A mutants. Animals with this large deletion are hypersensitive to the acetylcholinesterase inhibitor aldicarb but are unaffected by exogenous serotonin. Interestingly, this large klp-4 indel does not affect gross neuronal development but does lead to aggregation and disorganization of RAB-3 at synapses. Taken together, these data suggest a role for KLP-4 in modulation of cholinergic signaling in vivo and shed light on possible in vivo mechanisms of Kinesin-3 motor regulation.
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PMID:The Kinesin-3 motor, KLP-4, mediates axonal organization and cholinergic signaling in Caenorhabditis elegans. 3212 43