Sci. STKE, 4 January 2005
NEUROBIOLOGY Neuroligins Organize Excitatory and Inhibitory Postsynaptic Membranes
Neural connections require precise organization of the presynaptic and postsynaptic neurons. Neuroligins are transmembrane proteins expressed on the postsynaptic cell that bind to β-neurexins, which are presynaptic transmembrane proteins. Graf et al. report that β-neurexin is present in both excitatory (glutamatergic) and inhibitory (GABAergic) presynaptic neurons of the hippocampus. When these cells were plated with COS cells transfected to express neuroligin-1 or neuroligin-2, the presynaptic specializations that contained synaptic vesicles were induced in both types of axons. Coculture of fibroblasts expressing neurexin-1β with hippocampal neurons triggered the formation of PSD-95-positive or gephyrin-positive postsynaptic clusters in contacting dendrites (PSD-95 is an excitatory postsynaptic organizing protein and gephyrin is an inhibitory postsynaptic organizing protein). In addition, neurexin-1β stimulated clustering of N-methyl-D-aspartate (NMDA)-type glutamate receptor subunits and of GABAA receptor subunits. Analysis of the localization of neuroligin-1 (which is limited to excitatory postsynaptic membranes) and neuroligin-2, both of which bind neurexin, indicated that the majority of the gephyrin-positive clusters (inhibitory postsynaptic regions) were neuroligin-2 positive and that only about half of the PSD-95-positive clusters were also associated with neuroligin-2. To verify that clustering of neuroligins was the only requirement for the formation of postsynaptic specializations, neuroligin-1, -2, -3, or -4 was labeled with yellow fluorescent protein (YFP) and clustered using antibody against YFP. Neuroligin-1, -3, or -4 clustering produced PSD-95-positive structures, whereas neuroligin-2 clustering produced PSD-95- and gephyrin-positive structures. Thus, neuroligin isoform specificity contributes to the formation of excitatory or inhibitory postsynaptic structures.
E. R. Graf, X. Zhang, S.-X. Jin, M. W. Linhoff, A. M. Craig, Neurexins induce differentiation of GABA and glutamate postsynaptic specializations via neuroligins. Cell 119, 1013-1026 (2004). [PubMed]
Citation: Neuroligins Organize Excitatory and Inhibitory Postsynaptic Membranes. Sci. STKE 2005, tw8 (2005).
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