Nezha/CAMSAP3 and CAMSAP2 cooperate in epithelial-specific organization of noncentrosomal microtubules

Nezha/CAMSAP3 and CAMSAP2 cooperate in epithelial-specific organization of noncentrosomal microtubules
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DOI:
10.1073/pnas.1218017109
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发表时间:
2012-12-04
影响因子:
11.1
通讯作者:
Takeichi, Masatoshi
Takeichi, Masatoshi
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Tanaka, Nobutoshi;Meng, Wenxiang;Takeichi, Masatoshi

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与其他细胞类型的微管的中心辐射不同,上皮细胞中的主要微管不固定在中心体上。这些上皮性微管是如何在非中心体部位产生和稳定的还有待发现。在这里,我们发现哪吒[也被称为钙调蛋白调节的光影蛋白相关蛋白3(CAMSAP3)]及其相关蛋白CAMSAP2在非中心体微管的组织中相互作用。这两个CAMSAP分子聚集在非中心体微管的负端,从而稳定了它们。CAMSAPs的耗尽导致具有聚合加端的微管显著减少,同时诱导中心体中的微管生长。在CAMSAP耗竭的细胞中,早期内小体和高尔基体呈不规则分布。当两个CAMSAP都被移除时,CAMSAP耗竭的这些影响最大化。这些发现表明,CAMSAP2和-3共同维持非中心体微管,抑制中心体的微管组织能力,而CAMSAP锚定的微管网络对于细胞器的正确组装是重要的。
Major microtubules in epithelial cells are not anchored to the centrosome, in contrast to the centrosomal radiation of microtubules in other cell types. It remains to be discovered how these epithelial microtubules are generated and stabilized at noncentrosomal sites. Here, we found that Nezha [also known as calmodulin-regulated spectrin-associated protein 3 (CAMSAP3)] and its related protein, CAMSAP2, cooperate in organization of noncentrosomal microtubules. These two CAMSAP molecules coclustered at the minus ends of noncentrosomal microtubules and thereby stabilized them. Depletion of CAMSAPs caused a marked reduction of microtubules with polymerizing plus ends, concomitantly inducing the growth of microtubules from the centrosome. In CAMSAP-depleted cells, early endosomes and the Golgi apparatus exhibited irregular distributions. These effects of CAMSAP depletion were maximized when both CAMSAPs were removed. These findings suggest that CAMSAP2 and -3 work together to maintain noncentrosomal microtubules, suppressing the microtubule-organizing ability of the centrosome, and that the network of CAMSAP-anchored microtubules is important for proper organelle assembly.