Independent anterograde transport and retrograde cotransport of domain components of myelinated axons

Independent anterograde transport and retrograde cotransport of domain components of myelinated axons
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DOI:
10.1083/jcb.201906071
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发表时间:
2020-06-01
影响因子:
7.8
通讯作者:
Salzer, James L.
Salzer, James L.
中科院分区:
生物学1区
文献类型:
--
作者:
Bekku, Yoko;Salzer, James L.

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神经元是高度极化的细胞,组织成功能和分子上不同的结构域。一个关键的问题是,构成这些结构域的多蛋白复合物是作为一个复合物预先组装、运输和插入的,还是它们的组分是独立运输和局部组装的。在这里,我们对单独培养或与雪旺细胞一起培养的感觉神经元中兰维耶节点和其他有髓鞘轴突区域荧光标记成分的囊泡运输进行了动态成像,两两组合。一般来说,大多数蛋白质是在顺行方向上独立运输的。相反,由于轴突的共吞作用,来自不同结构域的蛋白质在逆行方向上有大量的共运输。早期髓鞘形成虽然增加了轴突运输囊泡的总数,但并没有实质性地改变这些运输模式。我们的研究结果表明,结构域成分在单独的囊泡中运输以进行局部组装,而不是预先形成的复合物,并且暗示轴突的内吞作用是一种清除机制。
Neurons are highly polarized cells organized into functionally and molecularly distinct domains. A key question is whether the multiprotein complexes that comprise these domains are preassembled, transported, and inserted as a complex or whether their components are transported independently and assemble locally. Here, we have dynamically imaged, in pairwise combinations, the vesicular transport of fluorescently tagged components of the nodes of Ranvier and other myelinated axonal domains in sensory neurons cultured alone or together with Schwann cells at the onset of myelination. In general, most proteins are transported independently in the anterograde direction. In contrast, there is substantial cotransport of proteins from distinct domains in the retrograde direction likely due to coendocytosis along the axon. Early myelination did not substantially change these patterns of transport, although it increased the overall numbers of axonal transport vesicles. Our results indicate domain components are transported in separate vesicles for local assembly, not as preformed complexes, and implicate endocytosis along axons as a mechanism of clearance.