GSK-3β-regulated interaction of BICD with dynein is involved in microtubule anchorage at centrosome
GSK-3β-regulated interaction of BICD with dynein is involved in microtubule anchorage at centrosome
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DOI：
10.1038/sj.emboj.7601459
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发表时间：
2006-12-13
期刊：
影响因子：
11.4
通讯作者：
Kikuchi, Akira
中科院分区：
文献类型：
--
作者：
Fumoto, Katsumi;Hoogenraad, Casper C.;Kikuchi, Akira
微管阵列指导细胞内组织并定义细胞极性。在这里，我们显示了一个新的功能，糖原合成酶激酶-3b（GSK-3b）的组织微管阵列通过与双尾-D（BICD）的相互作用。已知BICD与动力蛋白-动力肌动蛋白形成复合物，并在胞内囊泡运输中发挥作用。我们的数据显示，GSK-3b是BICD与动力蛋白结合所必需的，而不是与动力蛋白结合所必需的。GSK-3b或BICD的敲除减少了中心体聚焦的微管，并诱导了中心体蛋白的错误定位。GSK-3b敲除细胞中未聚焦的微管被动力蛋白中间链-BICD融合蛋白的表达所拯救。微管再生长试验表明，GSK-3b和BICD是微管锚定到中心体所必需的。这些结果表明，GSK-3b可能通过稳定BICD 1和动力蛋白复合物，将中心体蛋白转运到中心体，从而调节集中的微管组织。
Microtubule arrays direct intracellular organization and define cellular polarity. Here, we show a novel function of glycogen synthase kinase-3b (GSK-3b) in the organization of microtubule arrays through the interaction with Bicaudal-D (BICD). BICD is known to form a complex with dynein-dynactin and to function in the intracellular vesicle trafficking. Our data revealed that GSK-3b is required for the binding of BICD to dynein but not to dynactin. Knockdown of GSK-3b or BICD reduced centrosomally focused microtubules and induced the mislocalization of centrosomal proteins. The unfocused microtubules in GSK-3b knockdown cells were rescued by the expression of the dynein intermediate chain-BICD fusion protein. Microtubule regrowth assays showed that GSK-3b and BICD are required for the anchoring of microtubules to the centrosome. These results imply that GSK-3b may function in transporting centrosomal proteins to the centrosome by stabilizing the BICD1 and dynein complex, resulting in the regulation of a focused microtubule organization.