Cellular and Molecular Anatomy of the Human Neuromuscular Junction.
Cellular and Molecular Anatomy of the Human Neuromuscular Junction.
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DOI：
10.1016/j.celrep.2017.11.008
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发表时间：
2017-11-28
期刊：
影响因子：
8.8
通讯作者：
Gillingwater TH
中科院分区：
文献类型：
--
作者：
Jones RA;Harrison C;Eaton SL;Llavero Hurtado M;Graham LC;Alkhammash L;Oladiran OA;Gale A;Lamont DJ;Simpson H;Simmen MW;Soeller C;Wishart TM;Gillingwater TH
神经肌肉接头（NMJ）在下运动神经元向骨骼肌传递信息以产生运动的过程中起着重要作用。它也是一种实验上可获得的模型突触，通常在动物模型中进行研究，以探索突触形式和功能的基本方面。在这里，我们结合形态学技术，超分辨率成像和蛋白质组学分析，以揭示详细的细胞和分子结构的人NMJ。人类NMJ比小鼠NMJ明显更小，更不复杂，更碎片化。与小鼠相比，人类NMJ在整个成年期内也非常稳定，没有显示出与年龄相关的退化或重塑迹象。超分辨率成像和蛋白质组学分析显示，在人类NMJ的活性区蛋白和差异表达的核心突触蛋白和分子通路的独特分布。总之，这些发现揭示了NMJ的人类特异性细胞和分子特征，这些特征将它们与其他哺乳动物物种中的类似突触区分开来。人类神经肌肉接头（NMJ）在形态上与啮齿动物NMJ不同。人类NMJ在整个成人寿命中非常稳定。活性区蛋白，包括SNAP 25，在人类NMJ中差异定位。揭示了人类和低等哺乳动物的突触之间的根本差异。他们表明，人类神经肌肉接头（NMJ）比来自小鼠的类似突触更小，更碎片化，具有独特的分子组成。与小鼠相比，人类NMJ在整个成年期内也非常稳定。
The neuromuscular junction (NMJ) plays a fundamental role in transferring information from lower motor neuron to skeletal muscle to generate movement. It is also an experimentally accessible model synapse routinely studied in animal models to explore fundamental aspects of synaptic form and function. Here, we combined morphological techniques, super-resolution imaging, and proteomic profiling to reveal the detailed cellular and molecular architecture of the human NMJ. Human NMJs were significantly smaller, less complex, and more fragmented than mouse NMJs. In contrast to mice, human NMJs were also remarkably stable across the entire adult lifespan, showing no signs of age-related degeneration or remodeling. Super-resolution imaging and proteomic profiling revealed distinctive distribution of active zone proteins and differential expression of core synaptic proteins and molecular pathways at the human NMJ. Taken together, these findings reveal human-specific cellular and molecular features of the NMJ that distinguish them from comparable synapses in other mammalian species. Human neuromuscular junctions (NMJs) are morphologically distinct from rodent NMJs Human NMJs are remarkably stable across the adult lifespan Active zone proteins, including SNAP25, are differentially localized in human NMJs Significant divergence between the synaptic proteome of human and mouse NMJs Jones et al. reveal fundamental differences between synapses in humans and lower mammals. They show that human neuromuscular junctions (NMJs) are smaller and more fragmented than comparable synapses from mice, with a distinct molecular composition. In contrast to mice, human NMJs were also remarkably stable across the entire adult lifespan.
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DOI：
10.1002/jcsm.12121
发表时间：
2017-02
期刊：
Journal of cachexia, sarcopenia and muscle
影响因子：
--
作者：
Gonzalez-Freire M;Semba RD;Ubaida-Mohien C;Fabbri E;Scalzo P;Højlund K;Dufresne C;Lyashkov A;Ferrucci L
通讯作者：
Ferrucci L
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
7.7
作者：
Qiu, Jing;McQueen, Jamie;Hardingham, Giles E.
通讯作者：
Hardingham, Giles E.
DOI：
10.1073/pnas.1002220107
发表时间：
2010-08-17
影响因子：
11.1
作者：
Valdez, Gregorio;Tapia, Juan C.;Sanes, Joshua R.
通讯作者：
Sanes, Joshua R.
双色 STED 显微镜揭示了成年和老年小鼠活动区域中巴松管和短笛的三明治结构。
影响因子：
4.6
作者：
Nishimune H;Badawi Y;Mori S;Shigemoto K
通讯作者：
Shigemoto K