NGL family PSD-95-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

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181 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1294-1301
Number of pages8
JournalNature Neuroscience
Volume9
Issue number10
DOIs
Publication statusPublished - 2006 Oct

ASJC Scopus subject areas

  • Neuroscience(all)

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    Kim, S., Burette, A., Chung, H. S., Kwon, S. K., Woo, J., Lee, H. W., Kim, K., Kim, H., Weinberg, R. J., & Kim, E. (2006). NGL family PSD-95-interacting adhesion molecules regulate excitatory synapse formation. Nature Neuroscience, 9(10), 1294-1301. https://doi.org/10.1038/nn1763