Multiple MuSK signaling pathways and the aging neuromuscular junction.
Multiple MuSK signaling pathways and the aging neuromuscular junction.
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DOI：
10.1016/j.neulet.2020.135014
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发表时间：
2020-07-13
影响因子：
2.5
通讯作者：
Fallon JR
中科院分区：
文献类型：
--
作者：
Fish LA;Fallon JR
神经肌肉接头（NMJ）是运动神经元和肌肉之间快速、可靠和鲁棒通信的载体。这种突触的形态学，电生理学和遗传分析的无与伦比的可访问性已经产生了深入了解的许多分子组件介导其形成，成熟和稳定性。然而，围绕介导这些事件的信号通路以及它们如何在突触的整个生命周期中发挥作用的关键问题仍然没有答案。这些信息是至关重要的，因为NMJ是正常运动所必需的，并且在几种情况下受到损害，包括重症肌无力、肌萎缩性侧索硬化症（ALS）、脊髓性肌萎缩症（SMA）、肌营养不良症、肌肉减少症和衰老。肌肉特异性激酶（MuSK）是NMJ形成和稳定性的大多数（如果不是所有的话）环境中的核心参与者。然而，阐明这种受体在这一范围的设置中的功能是具有挑战性的，因为MuSK参与至少三个信号传导途径：作为一个酪氨酸激酶依赖性受体的聚集蛋白-LRP 4和Wnt;和，作为一个激酶非依赖性BMP共受体。在这里，我们专注于NMJ的稳定性在老化过程中，并讨论有关的分子机制，管理主动维护的NMJ，重点是MuSK和它的多个信号背景的潜在作用的开放性问题。
The neuromuscular junction (NMJ) is the vehicle for fast, reliable and robust communication between motor neuron and muscle. The unparalleled accessibility of this synapse to morphological, electrophysiological and genetic analysis has yielded an in depth understanding of many molecular components mediating its formation, maturation and stability. However, key questions surrounding the signaling pathways mediating these events and how they play out across the lifetime of the synapse remain unanswered. Such information is critical since the NMJ is necessary for normal movement and is compromised in several settings including myasthenia gravis, amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), muscular dystrophy, sarcopenia and aging. Muscle specific kinase (MuSK) is a central player in most if not all contexts of NMJ formation and stability. However, elucidating the function of this receptor in this range of settings is challenging since MuSK participates in at least three signaling pathways: as a tyrosine kinase-dependent receptor for agrin-LRP4 and Wnts; and, as a kinase-independent BMP co-receptor. Here we focus on NMJ stability during aging and discuss open questions regarding the molecular mechanisms that govern active maintenance of the NMJ, with emphasis on MuSK and the potential role of its multiple signaling contexts.
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