CRMP-2 binds to tubulin heterodimers to promote microtubule assembly
CRMP-2 binds to tubulin heterodimers to promote microtubule assembly
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DOI：
10.1038/ncb825
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发表时间：
2002-08-01
影响因子：
21.3
通讯作者：
Kaibuchi, K
中科院分区：
文献类型：
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作者：
Fukata, Y;Itoh, TJ;Kaibuchi, K
微管阵列形成的调节增加被认为对轴突生长很重要。坍缩反应介质蛋白-2 （CRMP-2）是哺乳动物UNC-33的同源物，其突变可导致异常轴突终止。我们最近证明了CRMP-2对轴突分化至关重要。在这里，我们确定了CRMP-2的两种活性：微管蛋白-异二聚体结合和促进微管组装。CRMP-2结合的微管蛋白二聚体比其结合的微管具有更高的亲和力。在CRMP-2存在的情况下，微管蛋白聚合增强了CRMP-2与微管的关联。CRMP-2与微管蛋白的结合特性与优先结合微管的Tau蛋白明显不同。在神经元中，过表达CRMP-2促进轴突生长和分支。CRMP-2突变体缺乏负责微管组装的区域，以显性负向方式抑制轴突生长和分支。综上所述，我们的研究结果表明，CRMP-2作为微管蛋白异源二聚体的伙伴，以不同于传统map的方式调节轴突生长和分支。
Regulated increase in the formation of microtubule arrays is thought to be important for axonal growth. Collapsin response mediator protein-2 (CRMP-2) is a mammalian homologue of UNC-33, mutations in which result in abnormal axon termination. We recently demonstrated that CRMP-2 is critical for axonal differentiation. Here, we identify two activities of CRMP-2: tubulin-heterodimer binding and the promotion of microtubule assembly. CRMP-2 bound tubulin dimers with higher affinity than it bound microtubules. Association of CRMP-2 with microtubules was enhanced by tubulin polymerization in the presence of CRMP-2. The binding property of CRMP-2 with tubulin was apparently distinct from that of Tau, which preferentially bound microtubules. In neurons, overexpression of CRMP-2 promoted axonal growth and branching. A mutant of CRMP-2, lacking the region responsible for microtubule assembly, inhibited axonal growth and branching in a dominant-negative manner. Taken together, our results suggest that CRMP-2 regulates axonal growth and branching as a partner of the tubulin heterodimer, in a different fashion from traditional MAPs.