Nature Neuroscience
- 9, 1294 - 1301 (2006)
Published online: 17 September 2006; | doi:10.1038/nn1763
NGL family PSD-95–interacting adhesion molecules regulate excitatory synapse formationSeho Kim1, Alain Burette2, Hye Sun Chung3, Seok-Kyu Kwon1, Jooyeon Woo1, Hyun Woo Lee1, Karam Kim1, Hyun Kim3, Richard J Weinberg2, 4 & Eunjoon Kim11
National Creative Research Initiative Center for Synaptogenesis and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea. 2
Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill, North Carolina 27599, USA. 3
Department of Anatomy and Division of Brain Korea 21, Biomedical Science, College of Medicine, Korea University, Seoul 136-705, Korea. 4
Neuroscience Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Correspondence should be addressed to Eunjoon Kim kime@kaist.ac.kr 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.
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