LIM Kinase 1 (LIMK1) Interacts with Tropomyosin-related Kinase B (TrkB) and Mediates Brain-derived Neurotrophic Factor (BDNF)-induced Axonal Elongation
LIM Kinase 1 (LIMK1) Interacts with Tropomyosin-related Kinase B (TrkB) and Mediates Brain-derived Neurotrophic Factor (BDNF)-induced Axonal Elongation
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LIM 激酶 1 (LIMK1) 与原肌球蛋白相关激酶 B (TrkB) 相互作用并介导脑源性神经营养因子 (BDNF) 诱导的轴突伸长
DOI：
10.1074/jbc.m112.405415
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发表时间：
2012-12-07
影响因子：
4.8
通讯作者：
Chen, Zhe-Yu
中科院分区：
文献类型：
--
作者：
Dong, Qing;Ji, Yun-Song;Chen, Zhe-Yu
BDNF/TrkB信号在神经元轴突生长中起着关键作用，其过程需要重塑细胞骨架结构，包括微管和丝状肌动蛋白。然而，BDNF/TrkB信号调节细胞骨架重组的机制仍不清楚。在这里，我们确定了LIMK 1和TrkB之间的新的相互作用，这是BDNF诱导的轴突伸长所必需的。我们证明了BDNF诱导的TrkB二聚化导致LIMK 1二聚化和转磷酸化，而不依赖于TrkB激酶活性，这可以进一步增强LIMK 1的激活和稳定。此外，激活LIMK 1易位到膜部分和磷酸化其底物cofilin，从而促进肌动蛋白聚合和轴突伸长。我们的研究结果为BDNF介导的信号转导导致轴突伸长提供了新的机制。
BDNF/TrkB signaling plays critical roles in axonal outgrowth of neurons, the process of which requires the remodeling of the cytoskeleton structure, including microtubules and filamentous actin. However, the mechanism by which BDNF/TrkB signaling regulates cytoskeleton reorganization is still unclear. Here, we identified a novel interaction between LIMK1 and TrkB, which is required for the BDNF-induced axonal elongation. We demonstrated that BDNF-induced TrkB dimerization led to LIMK1 dimerization and transphosphorylation independent of TrkB kinase activity, which could further enhance the activation and stabilization of LIMK1. Moreover, activated LIMK1 translocated to the membrane fraction and phosphorylated its substrate cofilin, thus promoting actin polymerization and axonal elongation. Our findings provided evidence of a novel mechanism for the BDNF-mediated signal transduction leading to axonal elongation.