神经元先天免疫、突触囊泡稳定和突触前内稳态可塑性的分子界面。
Molecular Interface of Neuronal Innate Immunity, Synaptic Vesicle Stabilization, and Presynaptic Homeostatic Plasticity.
机构信息
Department of Biochemistry and Biophysics, Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, CA 94158, USA.
Department of Biochemistry and Biophysics, Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, CA 94158, USA.
出版信息
Neuron. 2018 Dec 5;100(5):1163-1179.e4. doi: 10.1016/j.neuron.2018.09.048. Epub 2018 Oct 18.
We define a homeostatic function for innate immune signaling within neurons. A genetic analysis of the innate immune signaling genes IMD, IKKβ, Tak1, and Relish demonstrates that each is essential for presynaptic homeostatic plasticity (PHP). Subsequent analyses define how the rapid induction of PHP (occurring in seconds) can be coordinated with the life-long maintenance of PHP, a time course that is conserved from invertebrates to mammals. We define a novel bifurcation of presynaptic innate immune signaling. Tak1 (Map3K) acts locally and is selective for rapid PHP induction. IMD, IKKβ, and Relish are essential for long-term PHP maintenance. We then define how Tak1 controls vesicle release. Tak1 stabilizes the docked vesicle state, which is essential for the homeostatic expansion of the readily releasable vesicle pool. This represents a mechanism for the control of vesicle release, and an interface of innate immune signaling with the vesicle fusion apparatus and homeostatic plasticity.
我们定义了神经元内固有免疫信号的动态平衡功能。对固有免疫信号基因 IMD、IKKβ、Tak1 和 Relish 的遗传分析表明，每个基因对于突触前动态平衡可塑性（PHP）都是必需的。随后的分析定义了如何协调 PHP 的快速诱导（在几秒钟内发生）与 PHP 的终身维持，这一时间过程从无脊椎动物到哺乳动物都是保守的。我们定义了一个新的突触前固有免疫信号的分支。Tak1（Map3K）局部作用，对快速 PHP 诱导具有选择性。IMD、IKKβ 和 Relish 对于长期 PHP 维持是必需的。然后，我们定义了 Tak1 如何控制囊泡释放。Tak1 稳定停靠的囊泡状态，这对于可释放囊泡池的动态平衡扩展是必需的。这代表了一种控制囊泡释放的机制，以及固有免疫信号与囊泡融合装置和动态平衡可塑性的接口。
Zotero 插件