Amyloid precursor protein at node of Ranvier modulates nodal formation
Amyloid precursor protein at node of Ranvier modulates nodal formation
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DOI：
10.4161/cam.28802
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发表时间：
2014-07
影响因子：
3.2
通讯作者：
De-En Xu;Wen-Min Zhang;Zara Zhuyun Yang;Hong-mei Zhu;Ke Yan;Shao Li;D. Bagnard;G. Dawe;
中科院分区：
文献类型：
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作者：
De-En Xu;Wen-Min Zhang;Zara Zhuyun Yang;Hong-mei Zhu;Ke Yan;Shao Li;D. Bagnard;G. Dawe;
淀粉样前体蛋白(APP)通常与阿尔茨海默病相关，表达上调，沿受损轴突均匀分布，因此也被称为脱髓鞘轴突损伤和轴突变性的标志。然而，APP在有髓轴突上的生理分布和功能尚不清楚。我们报道APP聚集在有髓中枢神经系统(CNS)轴突的Ranvier(NOR)结节，但不聚集在外周神经系统(PNS)。在CNS NORs，APP的表达与Tenascin-R共定位，并伴随着并列联结的钾通道表达，表明APP定位于NOR。在APP基因敲除(KO)小鼠中，结节长度显著增加，而钠通道仍聚集在NORs处。此外，APP KO和APP过表达转基因(APP TG)小鼠的脊髓髓鞘厚度分别减少和增加，尽管与其产仔的WT小鼠相比变化有限。APPKO坐骨神经髓鞘厚度也较WT小鼠增加。我们的观察表明，APP在中枢神经系统NORs中作为一个新的成分，调节结节的形成，在促进髓鞘形成方面作用不大。
Amyloid precursor protein (APP), commonly associated with Alzheimer disease, is upregulated and distributes evenly along the injured axons, and therefore, also known as a marker of demyelinating axonal injury and axonal degeneration. However, the physiological distribution and function of APP along myelinated axons was unknown. We report that APP aggregates at nodes of Ranvier (NOR) in the myelinated central nervous system (CNS) axons but not in the peripheral nervous system (PNS). At CNS NORs, APP expression co-localizes with tenascin-R and is flanked by juxtaparanodal potassium channel expression demonstrating that APP localized to NOR. In APP-knockout (KO) mice, nodal length is significantly increased, while sodium channels are still clustered at NORs. Moreover, APP KO and APP-overexpressing transgenic (APP TG) mice exhibited a decreased and an increased thickness of myelin in spinal cords, respectively, although the changes are limited in comparison to their littermate WT mice. The thickness of myelin in APP KO sciatic nerve also increased in comparison to that in WT mice. Our observations indicate that APP acts as a novel component at CNS NORs, modulating nodal formation and has minor effects in promoting myelination.