Activity of all JNK isoforms contributes to neurite growth in spiral ganglion neurons.
Activity of all JNK isoforms contributes to neurite growth in spiral ganglion neurons.
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DOI：
10.1016/j.heares.2011.04.011
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发表时间：
2011-08
期刊：
影响因子：
2.8
通讯作者：
Green, Steven H.
中科院分区：
文献类型：
--
作者：
Atkinson, Patrick J.;Cho, Chang-Hyun;Hansen, Marlan R.;Green, Steven H.
Jun n -末端激酶（JNK）是一种多功能蛋白激酶，对神经元凋亡和神经突生长至关重要。我们之前已经证明，JNK活性与大鼠毛细胞丢失后的螺旋神经节神经元（SGN）凋亡相关，这意味着JNK抑制可能具有保护聋人SGN的治疗潜力。在这里，我们研究了JNK在培养的新生大鼠和小鼠sgn的神经突生长中的作用。我们发现JNK对于神经突的初始生长和已经建立的神经突的持续延伸是必需的。JNK抑制对神经突生长的影响是迅速的，并且在抑制剂洗脱后也迅速可逆。以phosphoJNK免疫反应性为指标，我们发现JNK在转移到缺乏神经营养刺激的培养基（5K培养基）后30分钟内在生长锥中被激活，但在细胞核和体细胞中激活需要数小时。通过将表位标记的JNK1， JNK2或JNK3亚型转染到sgn中，我们发现它们都存在于细胞核和细胞质中，并且在转移到5K培养基后没有优先重新分布到细胞核中。虽然单独转染dnJNK1或dnJNK2对神经突生长没有显著影响，但将显性阴性（dn） JNK1和JNK2共同转染sgn可减少神经突生长。JNK3−/−小鼠培养的sgn显示神经突生长减少，转染dnJNK1和dnJNK2进一步减少。这表明尽管JNK1和JNK2之间可能存在功能冗余，但所有三种JNK亚型都促进SGN神经突的生长。
Jun N-terminal kinase (JNK) is a multifunctional protein kinase crucial for neuronal apoptosis as well as neurite growth. We have previously shown that JNK activity is correlated with spiral ganglion neuron (SGN) apoptosis following hair cell loss in rats implying that JNK inhibition may have therapeutic potential to protect SGNs in deaf individuals. Here we investigated the role of JNK in neurite outgrowth from cultured neonatal rat and mouse SGNs. We show that JNK is required for initial growth of neurites and for continued extension of already established neurites. The effect of JNK inhibition on neurite growth is rapid and is also rapidly reversible after washout of the inhibitor. Using phosphoJNK immunoreactivity as an indicator, we show that JNK is activated in growth cones within 30 min after transfer to medium lacking neurotrophic stimuli (5K medium) but activation in the nucleus and soma requires hours. By transfecting epitope-tagged JNK1, JNK2, or JNK3 isoforms into SGNs, we found that all are present in the nucleus and cytoplasm and that there is no preferential redistribution to the nucleus after transfer to 5K medium. Cotransfection of dominant-negative (dn) JNK1 and JNK2 into SGNs reduced neurite growth, although transfection of dnJNK1 or dnJNK2 alone had no significant effect. SGNs cultured from JNK3−/− mice showed reduced neurite growth that was further reduced by transfection of dnJNK1 and dnJNK2. This indicates that all three JNK isoforms promote SGN neurite growth although there may be functional redundancy between JNK1 and JNK2.
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DOI：
10.1073/pnas.251194298
发表时间：
2001-11-20
影响因子：
11.1
作者：
Bennett, BL;Sasaki, DT;Anderson, DW
通讯作者：
Anderson, DW
影响因子：
9.2
作者：
Dajas-Ballador, Federico;Jones, Emma V.;Whitmarsh, Alan J.
通讯作者：
Whitmarsh, Alan J.
DOI：
10.1124/jpet.103.064246
发表时间：
2004-07-01
影响因子：
3.5
作者：
Carboni, S;Hiver, A;Vitte, PA
通讯作者：
Vitte, PA
影响因子：
5.3
作者：
Björkblom, B;Östman, N;Coffey, ET
通讯作者：
Coffey, ET
影响因子：
16.2
作者：
HAM, J;BABIJ, C;RUBIN, LL
通讯作者：
RUBIN, LL