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GSK-3β-regulated interaction of BICD with dynein is involved in microtubule anchorage at centrosome

机译:GSK-3β调节的BICD与动力蛋白的相互作用参与了中心体微管的锚定

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摘要

Microtubule arrays direct intracellular organization and define cellular polarity. Here, we show a novel function of glycogen synthase kinase-3β (GSK-3β) 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-3β is required for the binding of BICD to dynein but not to dynactin. Knockdown of GSK-3β or BICD reduced centrosomally focused microtubules and induced the mislocalization of centrosomal proteins. The unfocused microtubules in GSK-3β knockdown cells were rescued by the expression of the dynein intermediate chain-BICD fusion protein. Microtubule regrowth assays showed that GSK-3β and BICD are required for the anchoring of microtubules to the centrosome. These results imply that GSK-3β 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.
机译:微管阵列指导细胞内组织并定义细胞极性。在这里,我们展示了糖原合酶激酶3β(GSK-3β)在微管阵列中通过与比考达尔-D(BICD)相互作用的新型功能。已知BICD与动力蛋白-动力蛋白形成复合物,并在细胞内小泡运输中起作用。我们的数据表明,GSK-3β是BICD与动力蛋白结合而不是动力蛋白结合所必需的。击倒GSK-3β或BICD减少了中心体集中的微管并诱导了中心体蛋白质的错误定位。动力蛋白中间链-BICD融合蛋白的表达挽救了GSK-3β击倒细胞中未聚焦的微管。微管再生试验表明,GSK-3β和BICD是将微管锚定到中心体所必需的。这些结果暗示,GSK-3β可能通过稳定BICD1和动力蛋白复合物而在将中心体蛋白转运至中心体中发挥作用,从而导致聚焦的微管组织的调节。

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