Protein 4.1B contributes to the organization of peripheral myelinated axons.
Protein 4.1B contributes to the organization of peripheral myelinated axons.
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DOI：
10.1371/journal.pone.0025043
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Goutebroze L
中科院分区：
文献类型：
--
作者：
Cifuentes-Diaz C;Chareyre F;Garcia M;Devaux J;Carnaud M;Levasseur G;Niwa-Kawakita M;Harroch S;Girault JA;Giovannini M;Goutebroze L
神经元的特点是轴突极长。这种特殊的细胞形状可能取决于多种因素，包括细胞骨架和膜蛋白之间的相互作用。在许多细胞类型中，蛋白质4.1家族的成员在将皮质肌动蛋白-血影蛋白细胞骨架拴系到质膜上方面发挥重要作用。蛋白4.1B定位于有髓鞘轴突中，富集于结旁和结旁旁区，以及所有沿着节间，但不在Ranvier结，在Ranvier结中定位有负责动作电位传播的电压依赖性钠通道。为了阐明蛋白4.1B在有髓外周轴突的一般组织中的作用，我们研究了4.1B基因敲除小鼠。这些小鼠表现出轻度步态和运动性受损。而结未受影响，Caspr/paranodin的分布，锚定4.1B的膜，在paranodal区域，其水平降低。在黑腹果蝇中，Caspr 2（也与4.1B相互作用）以及相关的TAG-1和Kv1.1的富集在突变小鼠中不存在，而它们的水平没有改变。超微结构异常，观察到在paranodes和epartaparanodes。膈神经轴突口径略有减少，骨骼肌终末前运动轴突畸形。βII血影蛋白富集沿着轴膜减少。出生后3周的电生理记录显示，自发和诱发的重复活动的发生，表明神经元的过度兴奋，而没有改变传导速度。因此，我们的研究结果表明，在有髓鞘的轴突4.1B有助于在paranodes的膜蛋白的稳定，集群的arctaparanodal蛋白，和调节的节间轴突口径。
Neurons are characterized by extremely long axons. This exceptional cell shape is likely to depend on multiple factors including interactions between the cytoskeleton and membrane proteins. In many cell types, members of the protein 4.1 family play an important role in tethering the cortical actin-spectrin cytoskeleton to the plasma membrane. Protein 4.1B is localized in myelinated axons, enriched in paranodal and juxtaparanodal regions, and also all along the internodes, but not at nodes of Ranvier where are localized the voltage-dependent sodium channels responsible for action potential propagation. To shed light on the role of protein 4.1B in the general organization of myelinated peripheral axons, we studied 4.1B knockout mice. These mice displayed a mildly impaired gait and motility. Whereas nodes were unaffected, the distribution of Caspr/paranodin, which anchors 4.1B to the membrane, was disorganized in paranodal regions and its levels were decreased. In juxtaparanodes, the enrichment of Caspr2, which also interacts with 4.1B, and of the associated TAG-1 and Kv1.1, was absent in mutant mice, whereas their levels were unaltered. Ultrastructural abnormalities were observed both at paranodes and juxtaparanodes. Axon calibers were slightly diminished in phrenic nerves and preterminal motor axons were dysmorphic in skeletal muscle. βII spectrin enrichment was decreased along the axolemma. Electrophysiological recordings at 3 post-natal weeks showed the occurrence of spontaneous and evoked repetitive activity indicating neuronal hyperexcitability, without change in conduction velocity. Thus, our results show that in myelinated axons 4.1B contributes to the stabilization of membrane proteins at paranodes, to the clustering of juxtaparanodal proteins, and to the regulation of the internodal axon caliber.