LDL-receptor-related protein 4 is crucial for formation of the neuromuscular junction
LDL-receptor-related protein 4 is crucial for formation of the neuromuscular junction
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DOI：
10.1242/dev.02696
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发表时间：
2006-12-15
期刊：
影响因子：
4.6
通讯作者：
Niswander, Lee A.
中科院分区：
文献类型：
--
作者：
Weatherbee, Scott D.;Anderson, Kathryn V.;Niswander, Lee A.
低密度脂蛋白受体相关蛋白4(Low-Density Lipotein Receptor-Related Protein 4，Lrp4)是一类结构相关的单程跨膜蛋白家族成员，在发育和生理过程中具有多种功能，包括信号转导和受体介导的内吞作用。Lrp4在小鼠的多种组织中表达，对四肢、外胚层器官、肺和肾脏的正常发育和形态发生具有重要作用。我们发现Lrp4也在肌肉的突触后终板区域表达，是形成神经肌肉突触所必需的。Lrp4基因突变小鼠出生时就会死于突触前和突触后的分化缺陷，包括运动轴突生长和分支异常，缺乏乙酰胆碱受体和突触后蛋白聚集，以及不能通过肌纤维突触核选择性表达突触后基因。我们的数据表明，Lrp4在突触后神经肌肉连接(NMJ)形成的最早事件中是必需的，并提示它在NMJ组装的早期、非神经依赖步骤中起作用。确认Lrp4是NMJ形成的关键因素，可能对人类神经肌肉疾病，如肌无力综合征有意义。
Low-density lipoprotein receptor-related protein 4 (Lrp4) is a member of a family of structurally related, single-pass transmembrane proteins that carry out a variety of functions in development and physiology, including signal transduction and receptor-mediated endocytosis. Lrp4 is expressed in multiple tissues in the mouse, and is important for the proper development and morphogenesis of limbs, ectodermal organs, lungs and kidneys. We show that Lrp4 is also expressed in the post-synaptic endplate region of muscles and is required to form neuromuscular synapses. Lrp4-mutant mice die at birth with defects in both presynaptic and postsynaptic differentiation, including aberrant motor axon growth and branching, a lack of acetylcholine receptor and postsynaptic protein clustering, and a failure to express postsynaptic genes selectively by myofiber synaptic nuclei. Our data show that Lrp4 is required during the earliest events in postsynaptic neuromuscular junction (NMJ) formation and suggest that it acts in the early, nerve-independent steps of NMJ assembly. The identification of Lrp4 as a crucial factor for NMJ formation may have implications for human neuromuscular diseases such as myasthenia syndromes.