The synaptic adhesion molecules Neurexin and Neuroligin alter the development and function of synapses and are linked to autism in humans. In C. elegans, post-synaptic Neurexin (NRX-1) and pre-synaptic Neuroligin (NLG-1) mediate a retrograde synaptic signal that inhibits acetylcholine (ACh) release at neuromuscular junctions. Here, we show that the retrograde signal decreases ACh release by inhibiting the function of pre-synaptic UNC-2/CaV2 calcium channels. Post-synaptic NRX-1 binds to an auxiliary subunit of pre-synaptic UNC-2/CaV2 channels (UNC-36/alpha2delta), decreasing UNC-36 abundance at pre-synaptic elements. Retrograde inhibition is mediated by a soluble form of NRX-1's ectodomain, which is released from the post-synaptic membrane by the SUP-17/ADAM10 protease. Mammalian Neurexin-1alpha binds alpha2delta-3 and decreases CaV2.2 current in transfected cells, whereas Neurexin-1alpha has no effect on CaV2.2 reconstituted with alpha2delta-1 and alpha2delta-2. Collectively, these results suggest that alpha-Neurexin binding to alpha2delta is a conserved mechanism for regulating synaptic transmission.
        
Related information
Citations formats
Tong XJ, Lopez-Soto EJ, Li L, Liu H, Nedelcu D, Lipscombe D, Hu Z, Kaplan JM (2017) Retrograde Synaptic Inhibition Is Mediated by alpha-Neurexin Binding to the alpha2delta Subunits of N-Type Calcium Channels Neuron95: 326-340 e5
Tong XJ, Lopez-Soto EJ, Li L, Liu H, Nedelcu D, Lipscombe D, Hu Z, Kaplan JM (2017) Neuron95: 326-340 e5