Distribution of interleukin-1 receptor complex at the synaptic membrane driven by interleukin-1β and NMDA stimulation.
Distribution of interleukin-1 receptor complex at the synaptic membrane driven by interleukin-1β and NMDA stimulation.
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DOI：
10.1186/1742-2094-8-14
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发表时间：
2011-02-11
影响因子：
9.3
通讯作者：
Viviani B
中科院分区：
文献类型：
--
作者：
Gardoni F;Boraso M;Zianni E;Corsini E;Galli CL;Cattabeni F;Marinovich M;Di Luca M;Viviani B
白介素1受体(IL-1β，IL-1β)是一种促炎细胞因子，在多种退行性疾病中可导致神经元损伤，是一种潜在的治疗靶点。它通过激活白细胞介素1受体I型(IL-1RI)并招募由髓系分化主要反应蛋白88(MyD88)和IL-1R辅助蛋白(IL-1RAcP)组成的信号核心复合体来发挥其生物学效应。这一途径在外周免疫系统中已被清楚地描述，但关于其成员在神经细胞中的分子组成和分布，只有零星的信息可用。本研究结果表明，IL-1RI及其附属蛋白MyD88和IL-1RAcP在海马区和原代海马神经元的亚细胞室中的分布不同。特别是，只有IL-1RI在突触位置富含，在那里它与NMDA受体的GluN2B亚单位共定位并结合。此外，NMDA处理增加了IL-1RI与NMDA受体的相互作用，以及IL-1RI在突触膜上的表达和定位。IL-1β还可增加突触部位的IL-1RI水平，但不影响质膜上受体的总量。我们的结果首次揭示了N-甲基-D-天冬氨酸受体和IL-1RI系统之间存在动态和功能性的相互作用，这可能为IL-1β在依赖N-甲基-D-天冬氨酸受体激活的生理和病理事件中作为神经调节剂提供分子基础。
Interleukin-1β (IL-1β) is a pro-inflammatory cytokine that contributes to neuronal injury in various degenerative diseases, and is therefore a potential therapeutic target. It exerts its biological effect by activating the interleukin-1 receptor type I (IL-1RI) and recruiting a signalling core complex consisting of the myeloid differentiation primary response protein 88 (MyD88) and the IL-1R accessory protein (IL-1RAcP). This pathway has been clearly described in the peripheral immune system, but only scattered information is available concerning the molecular composition and distribution of its members in neuronal cells. The findings of this study show that IL-1RI and its accessory proteins MyD88 and IL-1RAcP are differently distributed in the hippocampus and in the subcellular compartments of primary hippocampal neurons. In particular, only IL-1RI is enriched at synaptic sites, where it co-localises with, and binds to the GluN2B subunit of NMDA receptors. Furthermore, treatment with NMDA increases IL-1RI interaction with NMDA receptors, as well as the surface expression and localization of IL-1RI at synaptic membranes. IL-1β also increases IL-1RI levels at synaptic sites, without affecting the total amount of the receptor in the plasma membrane. Our results reveal for the first time the existence of a dynamic and functional interaction between NMDA receptor and IL-1RI systems that could provide a molecular basis for IL-1β as a neuromodulator in physiological and pathological events relying on NMDA receptor activation.
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影响因子：
2.9
作者：
Liu, Song;Xu, Guo-Ying;McAdoo, David J.
通讯作者：
McAdoo, David J.
影响因子：
4.8
作者：
Viviani, Barbara;Gardoni, Fabrizio;Marinovich, Marina
通讯作者：
Marinovich, Marina
影响因子：
5.4
作者：
Korherr, C;Hofmeister, R;Falk, W
通讯作者：
Falk, W
影响因子：
5.3
作者：
Boutin, H;LeFeuvre, RA;Rothwell, NJ
通讯作者：
Rothwell, NJ
影响因子：
4.8
作者：
Burns, K;Martinon, F;Tschopp, J
通讯作者：
Tschopp, J