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Neuroligin 1 is dynamically exchanged at postsynaptic sites


Item Type:Article
Title:Neuroligin 1 is dynamically exchanged at postsynaptic sites
Creators Name:Schapitz, I.U. and Behrend, B. and Pechmann, Y. and Lappe-Siefke, C. and Kneussel, S.J. and Wallace, K.E. and Stempel, A.V. and Buck, F. and Grant, S.G.N. and Schweizer, M. and Schmitz, D. and Schwarz, J.R. and Holzbaur, E.L.F. and Kneussel, M.
Abstract:Neuroligins are postsynaptic cell adhesion molecules that associate with presynaptic neurexins. Both factors form a transsynaptic connection, mediate signaling across the synapse, specify synaptic functions, and play a role in synapse formation. Neuroligin dysfunction impairs synaptic transmission, disrupts neuronal networks, and is thought to participate in cognitive diseases. Here we report that chemical treatment designed to induce long-term potentiation or long-term depression (LTD) induces neuroligin 1/3 turnover, leading to either increased or decreased surface membrane protein levels, respectively. Despite its structural role at a crucial transsynaptic position, GFP-neuroligin 1 leaves synapses in hippocampal neurons over time with chemical LTD-induced neuroligin internalization depending on an intact microtubule cytoskeleton. Accordingly, neuroligin 1 and its binding partner postsynaptic density protein-95 (PSD-95) associate with components of the dynein motor complex and undergo retrograde cotransport with a dynein subunit. Transgenic depletion of dynein function in mice causes postsynaptic NLG1/3 and PSD-95 enrichment. In parallel, PSD lengths and spine head sizes are significantly increased, a phenotype similar to that observed upon transgenic overexpression of NLG1 (Dahlhaus et al., 2010). Moreover, application of a competitive PSD-95 peptide and neuroligin 1 C-terminal mutagenesis each specifically alter neuroligin 1 surface membrane expression and interfere with its internalization. Our data suggest the concept that synaptic plasticity regulates neuroligin turnover through active cytoskeleton transport.
Keywords:Biotinylation, Cultured Cells, Cytoskeleton, Dendritic Spines, Dyneins, Electrophysiology, Guanylate Kinase, Hippocampus, Immunohistochemistry, Immunoprecipitation, Intracellular Signaling Peptides and Proteins, Long-Term Potentiation, Long-Term Synaptic Depression, Mass Spectrometry, Membrane Proteins, Neuronal Cell Adhesion Molecules, Neurons, Synapses, Synaptic Transmission, Transfection, Animals, Mice
Source:Journal of Neuroscience
Publisher:Society for Neuroscience
Page Range:12733-12744
Date:22 September 2010
Official Publication:https://doi.org/10.1523/JNEUROSCI.0896-10.2010
PubMed:View item in PubMed

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