Post-translational regulation of Crmp in developing and regenerating chick spinal cord.
Post-translational regulation of Crmp in developing and regenerating chick spinal cord.
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Crmp 在鸡脊髓发育和再生中的翻译后调节。
DOI：
10.1002/dneu.20789
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发表时间：
2010
影响因子：
3
通讯作者：
Gögel S
中科院分区：
文献类型：
--
作者：
Gögel S
越来越明显的是，蛋白质水平的调控在发育和病理过程中起着至关重要的作用。因此，我们进行了蛋白质组学筛选，以确定鸡脊髓在发育阶段（E11）和再生阶段（E15）不同表达或修饰的蛋白质。在发育或脊髓损伤反应中受到调节的蛋白质包括坍缩反应介质蛋白（Crmps），已知其可调节微管动态和轴突生长。损伤后没有观察到显著的crmp转录本变化，表明主要在蛋白质水平上进行调控。对Crmp‐2蛋白及其磷酸化形式pS522和pT514的分析表明，Crmp‐2在发育过程中受到调节，并在体内神经祖细胞和神经球中表达。它的细胞定位随着发育和脊髓损伤而改变。此外，尽管Crmp‐2的总体表达水平不受损伤影响，但某些磷酸化形式的丰度发生了改变。pT514 Crmp‐2似乎与神经祖细胞的分裂有关，并且在非允许再生阶段大大减少，而它似乎不受损伤的影响。相反，2D Western blot显示，再生脊髓损伤后早期，S522处Crmp‐2的磷酸化水平上调，磷酸化与总Crmp‐2的比值增加。总之，本研究显示了在发育过程中Crmp - 2形式的高度动态调控，并确定了Crmp - 2翻译后的变化可能是维持脊髓再生能力的贡献者，可能是通过神经元细胞骨架的短暂稳定。©2010 Wiley期刊公司中国生物医学工程学报（英文版），2010
It is becoming apparent that regulation at the protein level plays crucial roles in developmental and pathological processes. Therefore, we performed a proteomics screen to identify proteins that are differently expressed or modified at stages of development permissive (E11) and nonpermissive for regeneration (E15) of the chick spinal cord. Proteins regulated either developmentally or in response to spinal‐cord injury included collapsin‐response‐mediator proteins (Crmps), known to modulate microtubule dynamic and axonal growth. No significant changes inCrmptranscripts following injury were observed, indicating regulation mainly at the protein level. Analysis of Crmp‐2 protein and its phosphorylated forms, pS522 and pT514, showed that Crmp‐2 is developmentally regulated and also expressed in neural progenitorsin vivoand in neurospheres. Its cellular localization changed both with development and following spinal‐cord injury. In addition, although overall levels of Crmp‐2 expression were not affected by injury, abundance of certain phosphorylated forms was altered. pT514 Crmp‐2 appeared to be associated with dividing neural progenitors and was greatly reduced at nonpermissive stages for regeneration, whereas it did not seem affected by injury. In contrast, phosphorylation of Crmp‐2 at S522 was upregulated early after injury in regenerating spinal cords and the ratio between phosphorylated to total Crmp‐2 increased, as indicated by 2D Western blots. Altogether, this study shows highly dynamic regulation of Crmp‐2 forms during development and identifies post‐translational changes in Crmp‐2 as putative contributors to the maintenance of spinal‐cord regenerative ability, possibly via a transient stabilization of the neuronal cytoskeleton. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 70: 456–471, 2010