Conservation and Innovation: Versatile Roles for LRP4 in Nervous System Development.
Conservation and Innovation: Versatile Roles for LRP4 in Nervous System Development.
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DOI：
10.3390/jdb9010009
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发表时间：
2021-03-14
影响因子：
2.7
通讯作者：
Mosca TJ
中科院分区：
文献类型：
--
作者：
DePew AT;Mosca TJ
随着神经系统的发展，神经元之间的连接必须形成，以实现有效的交流。突触发育的复杂过程需要伙伴神经元之间一系列复杂机制的协调，以确保突触前和突触后分化。这些机制中有许多是通过必需分泌因子和细胞表面受体的跨突触信号传导来促进突触发育的每一步。其中一种细胞表面受体LRP4作为突触组织者出现，在传递细胞外信号以启动发育过程中的多种细胞内事件中发挥关键作用。迄今为止，LRP4在哺乳动物神经肌肉连接发育中的作用广为人知，在那里它作为突触发生信号Agrin的受体调节突触发育。然而，最近，LRP4作为大脑中的突触组织者出现，在那里蛋白质的新功能不断出现，进一步增加了它已经多功能的作用的复杂性。其他研究结果表明，LRP4在神经系统疾病中发挥作用，包括重症肌无力、肌萎缩侧索硬化症和阿尔茨海默病，这表明需要进一步研究以了解疾病的病因。这篇综述将强调我们目前对LRP4在神经系统中的功能的了解，重点关注这种重要的细胞表面蛋白在不同的发育作用和不同的模式，以确保形成强大的突触连接。
As the nervous system develops, connections between neurons must form to enable efficient communication. This complex process of synaptic development requires the coordination of a series of intricate mechanisms between partner neurons to ensure pre- and postsynaptic differentiation. Many of these mechanisms employ transsynaptic signaling via essential secreted factors and cell surface receptors to promote each step of synaptic development. One such cell surface receptor, LRP4, has emerged as a synaptic organizer, playing a critical role in conveying extracellular signals to initiate diverse intracellular events during development. To date, LRP4 is largely known for its role in development of the mammalian neuromuscular junction, where it functions as a receptor for the synaptogenic signal Agrin to regulate synapse development. Recently however, LRP4 has emerged as a synapse organizer in the brain, where new functions for the protein continue to arise, adding further complexity to its already versatile roles. Additional findings indicate that LRP4 plays a role in disorders of the nervous system, including myasthenia gravis, amyotrophic lateral sclerosis, and Alzheimer’s disease, demonstrating the need for further study to understand disease etiology. This review will highlight our current knowledge of how LRP4 functions in the nervous system, focusing on the diverse developmental roles and different modes this essential cell surface protein uses to ensure the formation of robust synaptic connections.