Postsynaptic assembly induced by neurexin-neuroligin interaction and neurotransmitter.
Presynaptic and postsynaptic differentiation occurs at axodendritic contacts between CNS neurons. Synaptic adhesion mediated by synaptic cell adhesion molecule (SynCAM) and beta-neurexins/neuroligins triggers presynaptic differentiation. The signals that trigger postsynaptic differentiation are, however, unknown. Here we report that beta-neurexin expressed in nonneuronal cells induced postsynaptic density (PSD)-95 clustering in contacting dendrites of hippocampal neurons. The effect is specific to beta-neurexin and was not observed with other synaptic cell adhesion molecules such as N-cadherin or SynCAM. NMDA receptors, but not alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionate receptors (AMPARs), were recruited to this beta-neurexin-induced PSD-95 scaffold. Remarkably, AMPARs were inserted into this scaffold upon glutamate application or expression of a constitutively active form of calmodulin kinase II in neurons. Expression of a dominant-negative neuroligin-1 in cultured neurons markedly reduced the sizes and densities of PSD-95 puncta and AMPAR clusters. In addition, excitatory, but not inhibitory, synaptic functions were impaired in these neurons, confirming that PSD-95/neuroligin-1 interaction is involved in postsynaptic assembly at glutamatergic synapses. These results demonstrate that postsynaptic assembly of the glutamatergic synapse may be initiated by presynaptic beta-neurexin and that glutamate release also is required for maturation of synapses.
Nam
Christine I
CI
Department of Molecular and Cell Biology and Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720-3200, USA.
Chen
Lu
L
D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal; D002460:Cell Line; D002478:Cells, Cultured; D003001:Cloning, Molecular; D006624:Hippocampus / Q000502:physiology*; D006801:Humans; D007668:Kidney; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D016716:PC12 Cells; D051381:Rats; D018091:Receptors, AMPA / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D011994:Recombinant Proteins / Q000378:metabolism; D000074407:SAP90-PSD95 Associated Proteins
D015816:Cell Adhesion Molecules, Neuronal; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D011994:Recombinant Proteins; D000074407:SAP90-PSD95 Associated Proteins; C093438:neuroligin 1