Tubulin and CRMP-2 complex is transported via Kinesin-1

Tubulin and CRMP-2 complex is transported via Kinesin-1
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DOI:
10.1111/j.1471-4159.2005.03063.x
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发表时间:
2005-06-01
影响因子:
4.7
通讯作者:
Kaibuchi, K
Kaibuchi, K
中科院分区:
医学2区
文献类型:
--
作者:
Kimura, T;Arimura, N;Kaibuchi, K

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微管蛋白和微管在轴突生长中的运输对于轴突的生长和维持是必不可少的。然而,微管蛋白和微管与马达蛋白连接的分子机制尚不清楚。溃缩蛋白反应介导蛋白-2(CRMP-2)在原代海马神经元中富集于生长轴突的远端部分,并通过与微管蛋白二聚体和Numb的相互作用在轴突分化中起关键作用。在这项研究中,我们表明CRMP-2通过连接微管蛋白和驱动蛋白-1来调节微管蛋白转运。CRMP-2的C-末端区域直接结合驱动蛋白轻链1(KLC 1)的三肽重复结构域。可溶性微管蛋白与CRMP-2的中间结合,并与CRMP-2/KLC 1形成三聚体复合物。此外,GFP-微管蛋白在光漂白区域中的运动通过KLC或CRMP-2的敲低而减弱。这些结果表明,CRMP-2/驱动蛋白-1复合物调节可溶性微管蛋白运输到生长轴突的远端部分。
The transport of tubulin and microtubules in a growing axon is essential for axonal growth and maintenance. However, the molecular mechanism underlying the linkage of tubulin and microtubules to motor proteins is not yet clear. Collapsin response mediator protein-2 (CRMP-2) is enriched at the distal part of growing axons in primary hippocampal neurons and plays a critical role in axon differentiation through its interaction with tubulin dimer and Numb. In this study, we show that CRMP-2 regulates tubulin transport by linking tubulin and Kinesin-1. The C-terminal region of CRMP-2 directly binds to the tetratricopeptide repeat domain of kinesin light chain 1 (KLC1). Soluble tubulin binds to the middle of CRMP-2 and forms a trimeric complex with CRMP-2/KLC1. Furthermore, the movement of GFP-tubulin in the photobleached area is weakened by knockdown of KLCs or CRMP-2. These results indicate that the CRMP-2/Kinesin-1 complex regulates soluble tubulin transport to the distal part of the growing axon.