Local self-assembly mechanisms underlie the differential transformation of the proximal and distal cut axonal ends into functional and aberrant growth cones
Local self-assembly mechanisms underlie the differential transformation of the proximal and distal cut axonal ends into functional and aberrant growth cones
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DOI：
10.1002/cne.21522
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发表时间：
2008-03-01
影响因子：
2.5
通讯作者：
Spira, Micha E.
中科院分区：
文献类型：
--
作者：
Erez, Hadas;Spira, Micha E.
轴突切断后，近端和远端切断的轴突末端都转化为生长锥（GC）。而由近端节段的尖端形成的GC分支形成神经突，由远端切割端形成的结构不能生长。远端切割端形成异常GC的机制尚不清楚。前面我们描述了将近端切割轴突的尖端转化为GC的级联反应。这涉及微管（MT）极性重新取向，最终形成两个基于MT的囊泡陷阱，一个用于高尔基体衍生的囊泡，另一个保留逆行运输的囊泡。这些陷阱的形成是动态重聚合的MT和分子马达之间的局部相互作用的结果。高尔基体衍生的囊泡在正末端陷阱中的浓度对于成功产生功能性GC是必不可少的。通过在线共聚焦成像的横断培养的Aaplasia神经元，我们分析了在轴突切断后远端切断端的重建。我们发现最初近端和远端切割端发生相同的改变。然而，与近端相反，远端切割轴突仅形成一个负端MT为基础的陷阱，集中由负端定向电机驱动的内吞囊泡。然而，形成陷阱的MT使其正端离心指向以形成指状突起，被捕获的囊泡不能易位出来与质膜融合。因此，该结构形成在远端。切断的轴突不能支持生长过程。神经学比较杂志507：1019-1030，2008. (c)2007 Wiley-Liss，Inc.
Following axotomy, both the proximal and distal cut axonal ends transform into growth cones (GCs). Whereas the GCs formed by the tip of the proximal segment branch to form neurites, the structure formed by the distal cut end fails to grow. The mechanisms underlying the formation of an aberrant GC by the distal cut end are not understood. Earlier we described the cascade that transforms the tip of the proximal cut axon into a GC. This involves microtubule (MT) polar reorientation, which culminates in the formation of two MT-based vesicle traps, one for Golgi-derived vesicles and the other that retains retrogradely transported vesicles. The formation of these traps is the outcome of local interactions between dynamically repolymerizing MTs and molecular motors. The concentration of Golgi-derived vesicles in the plus-end trap is essential for the successful generation of a functional GC. By using online confocal imaging of transected cultured Aplysia neurons, we analyzed here the restructuring of the distal cut end after axotomy. We found that initially the proximal and distal cut ends undergo identical alterations. Nevertheless, in contrast to the proximal end, the distal cut axon forms only a minus-end MT-based trap that concentrates endocytotic vesicles driven by minus-end oriented motors. Whereas the MTs forming the trap polymerize pointing their plus-ends centrifugally to form finger-like protrusions, the trapped vesicles cannot translocate out to fuse with the plasma membrane. Thus, the structure formed at the distal. cut axon is incompetent to support growth processes. J. Comp. Neurol. 507:1019-1030, 2008. (c) 2007 Wiley-Liss, Inc.