Synaptic adhesion molecule IgSF11 regulates synaptic transmission and plasticity.
Synaptic adhesion molecule IgSF11 regulates synaptic transmission and plasticity.
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DOI：
10.1038/nn.4176
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发表时间：
2016-01
影响因子：
25
通讯作者：
Kim E
中科院分区：
文献类型：
--
作者：
Jang S;Oh D;Lee Y;Hosy E;Shin H;van Riesen C;Whitcomb D;Warburton JM;Jo J;Kim D;Kim SG;Um SM;Kwon SK;Kim MH;Roh JD;Woo J;Jun H;Lee D;Mah W;Kim H;Kaang BK;Cho K;Rhee JS;Choquet D;Kim E
突触粘附分子通过包括跨突触粘附和募集不同突触蛋白的机制来调节突触发育和可塑性。我们在这里报告的免疫球蛋白超家族成员11（IgSF 11），一个嗜同性的粘附分子优先在大脑中表达，是一种新的和双重结合的合作伙伴的突触后支架蛋白PSD-95和AMPAR谷氨酸受体（AMPAR）。IgSF 11需要PSD-95结合以用于其兴奋性突触定位。此外，IgSF 11稳定突触AMPAR，如通过高通量单分子追踪测量的IgSF 11敲低诱导的AMPAR介导的突触传递的抑制和AMPAR的表面迁移率增加所示。小鼠IgSF 11缺失导致齿状回AMPAR介导的突触传递抑制和海马CA 1区的长时程增强。IgSF 11不调节AMPAR的功能特征，包括脱敏、失活或恢复。这些结果表明，IgSF 11调节兴奋性突触传递和可塑性，通过其三方与PSD-95和AMPAR的相互作用。
Synaptic adhesion molecules regulate synapse development and plasticity through mechanisms including trans-synaptic adhesion and recruitment of diverse synaptic proteins. We report here that the immunoglobulin superfamily member 11 (IgSF11), a homophilic adhesion molecule preferentially expressed in the brain, is a novel and dual-binding partner of the postsynaptic scaffolding protein PSD-95 and AMPAR glutamate receptors (AMPARs). IgSF11 requires PSD-95 binding for its excitatory synaptic localization. In addition, IgSF11 stabilizes synaptic AMPARs, as shown 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 leads to suppression of AMPAR-mediated synaptic transmission in the dentate gyrus and long-term potentiation in the CA1 region of the hippocampus. IgSF11 does 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.