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.

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Publisher Full Text

Authors

Hu Z, Hom S, Kudze T, Tong XJ, Choi S, Aramuni G, Zhang W, Kaplan JM

Institution

Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.

Source

Science (New York, N.Y.) 337:6097 2012 Aug 24 pg 980-4

MeSH

Acetylcholine
Animals
Caenorhabditis elegans
Caenorhabditis elegans Proteins
Cell Adhesion Molecules, Neuronal
Cholinergic Neurons
Excitatory Postsynaptic Potentials
Exocytosis
Kinetics
Mice
MicroRNAs
Motor Neurons
Mutation
Neural Inhibition
Neuromuscular Junction
Neurotransmitter Agents
Synaptic Transmission
Synaptic Vesicles
Transcription Factors
Transfection

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

22859820