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Synaptic adhesion molecule IgSF11 regulates synaptic transmission and plasticity
Seil Jang1,16, Daeyoung Oh2,3,16, Yeunkum Lee4,16, Eric Hosy5,6,16, Hyewon Shin2, Christoph van Riesen7,
Daniel Whitcomb8,9, Julia M Warburton8, Jihoon Jo8,10, Doyoun Kim4, Sun Gyun Kim4, Seung Min Um1, Seok-kyu Kwon1, Myoung-Hwan Kim11,12, Junyeop Daniel Roh4, Jooyeon Woo1, Heejung Jun13, Dongmin Lee14, Won Mah15, Hyun Kim14, Bong-Kiun Kaang13, Kwangwook Cho8,9, Jeong-Seop Rhee7, Daniel Choquet5,6 & Eunjoon Kim1,4
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 knockdowninduced 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 characteristicsof 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.
npg 201 6 Nature America, Inc. All rights reserved.
Synaptic adhesion molecules regulate diverse aspects of synapse development and plasticity19. Mechanistically, trans-synaptic adhesions are thought to trigger the recruitment of a large number of pre- and postsynaptic cytoplasmic and membrane proteins, contributing to the formation of synapses. Some other synaptic adhesion molecules are thought to be targeted to synapses and contribute to the maintenance of synapses, by interacting with and stabilizing synaptic proteins. Given that postsynaptic receptors are important for the establishment, maintenance and plasticity of synaptic strength, synaptic adhesion molecules are expected to interact with postsynaptic receptors, but the molecular details are largely unclear.
Recent studies have described several interactions between synaptic adhesion molecules and postsynaptic receptors. One example is that between N-cadherin and AMPARs10,11, in which N-cadherin recruits AMPARs to excitatory synapses, decreases the surface mobility of AMPARs by immobilizing them at the synapse, and promotes GluA2 (a subunit of AMPARs)-dependent spine...