Regulation of excitatory synapse formationby the trans-synaptic adhesionbetween netrin-G and NGL

Abstract

Synaptic cell adhesion molecules (CAMs) regulate synapse formation through their trans-synaptic and heterophilic adhesion. Here we show that postsynaptic NGL CAMs associate with presynaptic netrin-G CAMs and, through their cytosolic tail, with the abundant postsynaptic scaffold PSD-95. Overexpression of NGL-2 in cultured neurons promotes excitatory postsynaptic differentiation. NGL-2 displayed on heterologous cells or beads induces presynaptic differentiation in contacting neurites. Direct aggregation of NGL-2 on the surface membrane of dendrites induces the clustering of excitatory postsynaptic proteins. Competitive inhibition by soluble NGL-2 reduces excitatory synapse numbers, and NGL-2 knockdown reduces excitatory synapse numbers and currents. These results suggest that the association between netrin-G, NGL, and PSD-95 selectively promotes the formation of excitatory, but not inhibitory, synapses.