title: Neurexin and neuroligin mediate retrograde synaptic inhibition in C. elegans.
abstract: The synaptic adhesion molecules neurexin and neuroligin alter the development and function of synapses and are linked to autism in humans. Here, we found that Caenorhabditis elegans neurexin (NRX-1) and neuroligin (NLG-1) mediated a retrograde synaptic signal that inhibited neurotransmitter release at neuromuscular junctions. Retrograde signaling was induced in mutants lacking a muscle microRNA (miR-1) and was blocked in mutants lacking NLG-1 or NRX-1. Release was rapid and abbreviated when the retrograde signal was on, whereas release was slow and prolonged when retrograde signaling was blocked. The retrograde signal adjusted release kinetics by inhibiting exocytosis of synaptic vesicles (SVs) that are distal to the site of calcium entry. Inhibition of release was mediated by increased presynaptic levels of tomosyn, an inhibitor of SV fusion.
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Zhitao
authors.initials: Z
authors.lastname: Hu
authors.forename: Sabrina
authors.initials: S
authors.lastname: Hom
authors.forename: Tambudzai
authors.initials: T
authors.lastname: Kudze
authors.forename: Xia-Jing
authors.initials: XJ
authors.lastname: Tong
authors.forename: Seungwon
authors.initials: S
authors.lastname: Choi
authors.forename: Gayane
authors.initials: G
authors.lastname: Aramuni
authors.forename: Weiqi
authors.initials: W
authors.lastname: Zhang
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Kaplan
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D059329:Cholinergic Neurons / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials; D005089:Exocytosis; D007700:Kinetics; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D009046:Motor Neurons / Q000502:physiology; D009154:Mutation; D009433:Neural Inhibition; D009469:Neuromuscular Junction / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000378:metabolism; D009435:Synaptic Transmission; D013572:Synaptic Vesicles / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D029742:Caenorhabditis elegans Proteins; D015816:Cell Adhesion Molecules, Neuronal; D035683:MicroRNAs; D018377:Neurotransmitter Agents; D014157:Transcription Factors; C518291:mef-2 protein, C elegans; C093438:neuroligin 1; C574757:nrx-1 protein, C elegans; C513301:tom-1 protein, C elegans; D000109:Acetylcholine