Neurexin and neuroligin mediate retrograde synaptic inhibition in C. elegans.
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.
Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
SourceScience (New York, N.Y.) 337:6097 2012 Aug 24 pg 980-4
Caenorhabditis elegans Proteins
Cell Adhesion Molecules, Neuronal
Excitatory Postsynaptic Potentials
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.