Developmental analysis of Lingo-1/Lern1 protein expression in the mouse brain:: Interaction of its intracellular domain with Myt1l
Developmental analysis of Lingo-1/Lern1 protein expression in the mouse brain:: Interaction of its intracellular domain with Myt1l
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DOI：
10.1002/dneu.20607
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发表时间：
2008-03-01
影响因子：
3
通讯作者：
Sumoy, Lauro
中科院分区：
文献类型：
--
作者：
Llorens, Franc;Gil, Vanesa;Sumoy, Lauro
Lingo-1（也称为Lern 1）是Nogo受体复合物的一种组分，其介导响应髓鞘相关抑制剂（迈斯）的细胞内信号传导：NogoA、MAG和Omgp。通过Nogo受体的信号传导不仅限于其在CNS损伤后防止轴突再生的众所周知的作用，还涉及神经元功能成熟。使用Lingo-1缺陷小鼠，已经证明Lingo-1在脑发育期间的少突胶质细胞分化中起相关作用，并且用Lingo-1拮抗剂治疗可以通过减少MAI介导的信号传导来改善成年小鼠损伤后的轴突再生。然而，Lingo-1蛋白与Nogo受体其他伙伴相关的表达模式的详细描述缺失。在这里，我们表明，Nogo受体复合物，Lingo-1，NgR 1，p75和TROY的成分共存于小鼠大脑中的一个定义的时间窗口，只有在出生后的后期阶段。我们还确定了Lingo-1的分布，显示在特定的神经元亚群中表达，但不在髓鞘成熟的少突胶质细胞中表达。令人惊讶的是，Lingo-1在没有NgR 1的早期发育阶段表达，这支持了Lingo-1可能参与发育中的神经元的其他活动的观点，这些活动不同于成年人中的少突胶质细胞成熟或轴突延伸抑制。最后，我们提出，Lingo-1的细胞内结构域有助于信号传导，并表明它与有丝分裂后神经元特异性锌指蛋白Myt 1 l相互作用，这表明Lingo-1可能通过影响其亚细胞定位来调节Myt 1 l转录因子的活性。(C)2008 Wiley Periodicals，Inc.
Lingo-1 (also known as Lern1) is a component of the Nogo receptor complex that mediates intracellular signaling in response to myelin associated inhibitors (MAIs): NogoA, MAG, and Omgp. Signaling through Nogo receptor extends to more than its well known role in preventing axon regeneration after lesion in the CNS, being implicated in neuronal functional maturation. Using Lingo-1-deficient mice, it has been demonstrated that Lingo-1 plays relevant roles in oligodendrocyte differentiation during brain development, and that treatment with Lingo-1 antagonists can improve axon regeneration after lesion in adult mice by decreasing MAI mediated signaling. However, a detailed description of the pattern of expression of Lingo-1 protein in correlation with the other partners of Nogo receptor is missing. Here, we show that components of the Nogo receptor complex, Lingo-1, NgR1, p75, and TROY coexist in mouse brain in a defined time window only at later postnatal stages. We have also determined the Lingo-1 distribution showing expression in particular subsets of neurons, but not in myelinating mature oligodendrocytes. Surprisingly, Lingo-1 is expressed at early developmental stages without NgR1, which supports the notion that Lingo-1 may participate in other activities in developing neurons different from oligodendrocyte maturation or axon extension inhibition in the adult. Finally, we propose that the intracellular domain of Lingo-1 contributes to signaling and show that it interacts with the postmitotic neuronal specitic zinc finger protein Myt1l, suggesting that Lingo-1 may regulate Myt1l transcription factor activity by affecting its subcellular localization. (C) 2008 Wiley Periodicals, Inc.