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Synaptic adhesion molecule IgSF11 regulates synaptic transmission and plasticity
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Journal Article
Synaptic adhesion molecule IgSF11 regulates synaptic transmission and plasticity
2016
Overview
Synaptic adhesion molecules are known to regulate synapse development, but growing evidence indicates that they also regulate synaptic function and plasticity. The authors report a novel synaptic adhesion molecule, IgSF11, that regulates excitatory synaptic transmission and plasticity through its dual interaction with the postsynaptic scaffold PSD-95 and AMPA receptors.
Synaptic adhesion molecules regulate synapse development and plasticity through mechanisms that include trans-synaptic adhesion and recruitment of diverse synaptic proteins. We found that the immunoglobulin superfamily member 11 (IgSF11), a homophilic adhesion molecule that preferentially expressed in the brain, is a dual-binding partner of the postsynaptic scaffolding protein PSD-95 and AMPA glutamate receptors (AMPARs). IgSF11 required PSD-95 binding for its excitatory synaptic localization. In addition, IgSF11 stabilized synaptic AMPARs, as determined by IgSF11 knockdown–induced suppression of AMPAR-mediated synaptic transmission and increased surface mobility of AMPARs, measured by high-throughput, single-molecule tracking. IgSF11 deletion in mice led to the suppression of AMPAR-mediated synaptic transmission in the dentate gyrus and long-term potentiation in the CA1 region of the hippocampus. IgSF11 did not regulate the functional characteristics of AMPARs, including desensitization, deactivation or recovery. These results suggest that IgSF11 regulates excitatory synaptic transmission and plasticity through its tripartite interactions with PSD-95 and AMPARs.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ 64/60
/ 82/80
/ 9/74
/ Adhesion
/ Animal Genetics and Genomics
/ Animals
/ Brain
/ Cell Adhesion Molecules - metabolism
/ Cell Adhesion Molecules - physiology
/ Cell Adhesion Molecules, Neuronal - physiology
/ Disks Large Homolog 4 Protein
/ Gene Expression Regulation - physiology
/ Humans
/ Immunoglobulins - metabolism
/ Immunoglobulins - physiology
/ Intracellular Signaling Peptides and Proteins - metabolism
/ Medicine
/ Membrane Proteins - metabolism
/ Mice
/ Neuronal Plasticity - physiology
/ Proteins
/ Rabbits
/ Rats
/ Receptors, AMPA - metabolism
/ Science
