title: A neuropeptide-mediated stretch response links muscle contraction to changes in neurotransmitter release.
abstract: Although Caenorhabditis elegans has been utilized extensively to study synapse formation and function, relatively little is known about synaptic plasticity in C. elegans. We show that a brief treatment with the cholinesterase inhibitor aldicarb induces a form of presynaptic potentiation whereby ACh release at neuromuscular junctions (NMJs) is doubled. Aldicarb-induced potentiation was eliminated by mutations that block processing of proneuropeptides, by mutations inactivating a single proneuropeptide (NLP-12), and by those inactivating an NLP-12 receptor (CKR-2). NLP-12 expression is limited to a single stretch-activated neuron, DVA. Analysis of a YFP-tagged NLP-12 suggests that aldicarb stimulates DVA secretion of NLP-12. Mutations disrupting the DVA mechanoreceptor (TRP-4) decreased aldicarb-induced NLP-12 secretion and blocked aldicarb-induced synaptic potentiation. Mutants lacking NLP-12 or CKR-2 have decreased locomotion rates. Collectively, these results suggest that NLP-12 mediates a mechanosensory feedback loop that couples muscle contraction to changes in presynaptic release, thereby providing a mechanism for proprioceptive control of locomotion.
authors: Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
authors: Zhitao
authors: Z
authors: Hu
authors: Edward C G
authors: EC
authors: Pym
authors: Kavita
authors: K
authors: Babu
authors: Amy B
authors: AB
authors: Vashlishan Murray
authors: Joshua M
authors: JM
authors: Kaplan
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000448:Aldicarb / Q000494:pharmacology; D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D053444:Inhibitory Postsynaptic Potentials / Q000235:genetics / Q000502:physiology; D008124:Locomotion / Q000502:physiology; D008465:Mechanoreceptors / Q000378:metabolism* / Q000502:physiology; D009119:Muscle Contraction / Q000502:physiology*; D009154:Mutation; D009473:Neuronal Plasticity / Q000235:genetics / Q000502:physiology*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D045706:Proprotein Convertase 2 / Q000235:genetics; D054390:Receptors, CCR2 / Q000235:genetics; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D050052:TRPC Cation Channels / Q000235:genetics
chemical_list: D029742:Caenorhabditis elegans Proteins; D002800:Cholinesterase Inhibitors; D009479:Neuropeptides; D054390:Receptors, CCR2; C509780:TRP-4 channel, C elegans; D050052:TRPC Cation Channels; D000448:Aldicarb; C473666:EGL-3 proprotein convertase, C elegans; D045706:Proprotein Convertase 2; D000109:Acetylcholine