A Novel c-Jun N-terminal Kinase (JNK) Signaling Complex Involved in Neuronal Migration during Brain Development
A Novel c-Jun N-terminal Kinase (JNK) Signaling Complex Involved in Neuronal Migration during Brain Development
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一种新型 c-Jun N 末端激酶 (JNK) 信号复合物参与大脑发育过程中的神经元迁移
DOI：
10.1074/jbc.m116.716811
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发表时间：
2016-05-27
影响因子：
4.8
通讯作者：
Xu, Zhiheng
中科院分区：
文献类型：
--
作者：
Zhang, Feng;Yu, Jingwen;Xu, Zhiheng
神经元迁移障碍可引起各种神经系统疾病。转化生长因子-β（TGF-β）信号和微脑相关蛋白WDR 62在脑发育过程中对神经元迁移都很重要;然而，所涉及的潜在分子机制仍不清楚。我们在这里表明，敲除或敲低的Tak 1（TGF β激活激酶1）和JNK 2（c-Jun N-末端激酶2）干扰皮质发育过程中的神经元迁移和迁移缺陷所引起的敲除和/或敲低的T β r2（II型TGF-β受体）或Tak 1可以部分拯救的表达TAK 1和JNK 2，分别。此外，TAK 1与RAC 1和JNK途径的两个支架蛋白，即小脑相关蛋白WDR 62和RAC 1相互作用蛋白POSH（大量Src同源性）形成蛋白质复合物。复合物的组分在TAK 1以及JNK活性的调节中相互协调。我们认为，独特的JNK蛋白复合物参与了脑发育和疾病发病过程中的多种生物学和病理学功能。
Disturbance of neuronal migration may cause various neurological disorders. Both the transforming growth factor-beta (TGF-beta) signaling and microcephaly-associated protein WDR62 are important for neuronal migration during brain development; however, the underlying molecular mechanisms involved remain unclear. We show here that knock-out or knockdown of Tak1 (TGF beta-activated kinase 1) and Jnk2 (c-Jun N-terminal kinase 2) perturbs neuronal migration during cortical development and that the migration defects incurred by knock-out and/or knockdown of T beta r2 (type II TGF-beta receptor) or Tak1 can be partially rescued by expression of TAK1 and JNK2, respectively. Furthermore, TAK1 forms a protein complex with RAC1 and two scaffold proteins of the JNK pathway, the microcephaly-associated protein WDR62 and the RAC1-interacting protein POSH (plenty of Src homology). Components of the complex coordinate with each other in the regulation of TAK1 as well as JNK activities. We suggest that unique JNK protein complexes are involved in the diversified biological and pathological functions during brain development and pathogenesis of diseases.