Kim Seho, Burette Alain, Chung Hye Sun, Kwon Seok-Kyu, Woo Jooyeon, Lee Hyun Woo, Kim Karam, Kim Hyun, Weinberg Richard J, Kim Eunjoon
National Creative Research Initiative Center for Synaptogenesis and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
Nat Neurosci. 2006 Oct;9(10):1294-301. doi: 10.1038/nn1763. Epub 2006 Sep 17.
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.
突触细胞黏附分子（CAMs）通过其跨突触和异嗜性黏附作用来调节突触形成。在此我们表明，突触后网蛋白-G配体（NGL）CAMs以一种亚型特异性方式与网蛋白-G CAMs结合，并通过其胞质尾部与丰富的突触后支架突触后致密蛋白95（PSD-95）相结合。在培养的大鼠神经元中过表达NGL-2增加了PSD-95阳性树突棘的数量。位于异源细胞或珠子上的NGL-2在接触的神经突中诱导功能性突触前分化。NGL-2在树突表面膜上的直接聚集诱导了兴奋性突触后蛋白的聚集。可溶性NGL-2的竞争性抑制减少了兴奋性突触的数量。敲低NGL-2减少了兴奋性突触而非抑制性突触的数量和电流。这些结果表明NGL调节兴奋性突触的形成。
