Neuroligin 1 is dynamically exchanged at postsynaptic sites

Schapitz, I.U.; Behrend, B.; Pechmann, Y.; Lappe-Siefke, C.; Kneussel, S.J.; Wallace, K.E.; Stempel, A.V.; Buck, F.; Grant, S.G.N.; Schweizer, M.; Schmitz, D.; Schwarz, J.R.; Holzbaur, E.L.F.; Kneussel, M.

Neuroligin 1 is dynamically exchanged at postsynaptic sites

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Item Type:	Article
Title:	Neuroligin 1 is dynamically exchanged at postsynaptic sites
Creators Name:	Schapitz, I.U., Behrend, B., Pechmann, Y., Lappe-Siefke, C., Kneussel, S.J., Wallace, K.E., Stempel, A.V., Buck, F., Grant, S.G.N., Schweizer, M., Schmitz, D., Schwarz, J.R., 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
ISSN:	0270-6474
Publisher:	Society for Neuroscience
Volume:	30
Number:	38
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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