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Nature Neuroscience 9, 1294–1301 (1 October 2006) | doi:10.1038/nn1763

NGL family PSD-95|[ndash]|interacting adhesion molecules regulate excitatory synapse formation

Seho Kim , Alain Burette , Hye Sun Chung , Seok-Kyu Kwon , Jooyeon Woo , Hyun Woo Lee , Karam Kim , Hyun Kim , Richard J Weinberg & Eunjoon Kim

Synaptic cell adhesion molecules (CAMs) regulate synapse formation through their trans-synaptic and heterophilic adhesion. Here we show that postsynaptic netrin-G ligand (NGL) CAMs associate with netrin-G CAMs in an isoform-specific manner and, through their cytosolic tail, with the abundant postsynaptic scaffold postsynaptic density–95 (PSD-95). Overexpression of NGL-2 in cultured rat neurons increased the number of PSD-95–positive dendritic protrusions. NGL-2 located on heterologous cells or beads induced functional presynaptic differentiation in contacting neurites. Direct aggregation of NGL-2 on the surface membrane of dendrites induced the clustering of excitatory postsynaptic proteins. Competitive inhibition by soluble NGL-2 reduced the number of excitatory synapses. NGL-2 knockdown reduced excitatory, but not inhibitory, synapse numbers and currents. These results suggest that NGL regulates the formation of excitatory synapses.