Vimentin-dependent spatial translocation of an activated MAP kinase in injured nerve
Vimentin-dependent spatial translocation of an activated MAP kinase in injured nerve
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DOI：
10.1016/j.neuron.2005.01.023
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发表时间：
2005-03-03
期刊：
影响因子：
16.2
通讯作者：
Fainzilber, M
中科院分区：
文献类型：
--
作者：
Perlson, E;Hanz, S;Fainzilber, M
例如在神经损伤后轴突到细胞体的信号转导中，磷酸化的激酶是如何在长时间的细胞内运输的？在这里，我们发现，在神经损伤时，MAP激酶ERK1和ERK2在坐骨神经轴浆中被磷酸化，同时伴随着中间细丝波形蛋白的局部翻译和钙蛋白在轴浆中的裂解而产生的可溶性形式。Vimentin结合磷酸化ERK(PERK)，从而通过直接结合Vimentin和Importin P将PERK连接到动力蛋白逆行运动。在Vimentin缺失小鼠的背根神经节神经元中，损伤诱导的ELK1激活和神经元再生被抑制或延迟，在用MEK抑制剂或阻止PERK-Vimentin结合的多肽处理的大鼠中。因此，可溶性波形蛋白使受损神经中的PERK通过重要蛋白和动力蛋白发生空间移位。
How are phosphorylated kinases transported over long intracellular distances, such as in the case of axon to cell body signaling after nerve injury? Here, we show that the MAP kinases Erk1 and Erk2 are phosphorylated in sciatic nerve axoplasm upon nerve injury, concomitantly with the production of soluble forms of the intermediate filament vimentin by local translation and calpain cleavage in axoplasm. Vimentin binds phosphorylated Erks (pErk), thus linking pErk to the dynein retrograde motor via direct binding of vimentin to importin P. Injury-induced Elk1 activation and neuronal regeneration are inhibited or delayed in dorsal root ganglion neurons from vimentin null mice, and in rats treated with a MEK inhibitor or with a peptide that prevents pErk-vimentin binding. Thus, soluble vimentin enables spatial translocation of pErk by importins and dynein in lesioned nerve.