Local calcium-dependent mechanisms determine whether a cut axonal end assembles a retarded endbulb or competent growth cone
Local calcium-dependent mechanisms determine whether a cut axonal end assembles a retarded endbulb or competent growth cone
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DOI：
10.1016/j.expneurol.2009.05.004
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发表时间：
2009-09-01
影响因子：
5.3
通讯作者：
Spira, Micha E.
中科院分区：
文献类型：
--
作者：
Kamber, Dotan;Erez, Hadas;Spira, Micha E.
轴突切断后，切断的轴突末端转化为生长锥（GC）是导致再生的级联反应中的关键事件。在较早的一系列研究中，我们分析了将切断的轴突末端转化为感受态GC的细胞级联。我们发现，轴突切断培养的脊髓神经元导致细胞内游离Ca ~（2+）浓度（[Ca ~（2+）]（i））的短暂升高，钙蛋白酶激活和膜下血影蛋白的局部蛋白水解。这些事件与不同的基于微管（MT）的囊泡陷阱的形成有关，所述囊泡陷阱积累顺行运输的囊泡，所述囊泡与无血影蛋白的质膜融合以支持生长过程（Erez，H.，Malkinson，G.，Prager-Khoutorsky，M.，De Zeeuw，C. I.，Hoogenraad，C.C.，和Spira，M.E. 2007.基于微管的陷阱的形成控制了轴突切断后再生神经元的限制性位点的囊泡的分选和浓缩。J. Cell Biol.176：497-507.：埃雷兹，H.，和Spira，M.E. 2008.局部自组装机制是近端和远端切断轴突末端分化为功能性和异常生长锥的基础。J. Comp.神经元507：spc1.）。在这里，我们报告说，在限制钙流入切断轴突末端的条件下，轴突切断导致形成endbulls（EB），而不是主管GC。在这些条件下，典型的基于MT的囊泡陷阱不形成，并且高尔基体衍生的囊泡集中在切割轴突的最尖端。由于在这些条件下血影蛋白屏障不被切割，囊泡与质膜的融合和肌动蛋白聚合被延迟，生长过程受到损害。我们的结论是，主管GC或EB轴突切断后的立即组装是由损伤部位的[Ca 2 +]（i）梯度的大小塑造的自主局部事件的结果。(C)2009 Elsevier Inc. All rights reserved.
The transformation of a cut axonal end into a growth cone (GC), after axotomy, is a critical event in the cascade leading to regeneration. in an earlier series of studies we analyzed the cellular cascades that transform a cut axonal end into a competent GC. We found that axotomy of cultured Aplysia neurons leads to a transient elevation of the free intracellular Ca2+ concentration ([Ca2+](i)), calpain activation and localized proteolysisofsubmembranal spectrin. These events are associated with the formation of distinct microtubule (MT) based vesicle traps that accumulate anterogradely transported vesicles that fuse with the spectrin free plasma membrane in support of the growth process (Erez, H., Malkinson, G., Prager-Khoutorsky, M., De Zeeuw, C.I., Hoogenraad, C.C., and Spira, M.E. 2007. Formation of microtubule-based traps controls the sorting and concentration of vesicles to restricted sites of regenerating neurons after axotomy. J. Cell Biol. 176: 497-507.: Erez, H., and Spira, M.E. 2008. Local self-assembly mechanisms underlie the differential transformation of the proximal and distal cut axonal ends into functional and aberrant growth cones. J. Comp. Neurol. 507: spc1.). Here we report that under conditions that limit calcium influx into the cut axonal end, axotomy leads to the formation of endbulbs (EBs) rather than to competent GCs. Under these conditions typical MT based vesicle traps are not formed, and Golgi derived vesicles concentrate at the very tip of the cut axon. Since under these conditions the spectrin barrier is not cleaved, vesicle fusion with the plasma membrane and actin polymerization are retarded and growth processes are impaired. We conclude that the immediate assembly of competent GC or an EB after axotomy is the outcome of autonomous local events that are shaped by the magnitudes of the [Ca2+](i) gradients at the site of injury. (C) 2009 Elsevier Inc. All rights reserved.