Importin alpha transports CaMKIV to the nucleus without utilizing importin beta.
Importin alpha transports CaMKIV to the nucleus without utilizing importin beta.
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发表时间：
2005
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通讯作者：
I. Kotera;T. Sekimoto;Y. Miyamoto;T. Saiwaki;E. Nagoshi;H. Sakagami;H. Kondo;Y. Yoneda
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作者：
I. Kotera;T. Sekimoto;Y. Miyamoto;T. Saiwaki;E. Nagoshi;H. Sakagami;H. Kondo;Y. Yoneda
Ca(2+)/钙调蛋白依赖的蛋白激酶IV(CaMKIV)在cAMP反应元件结合蛋白介导的信号通路的转录激活中起重要作用。尽管CaMKIV主要定位于细胞核，但CaMKIV核输入的分子机制尚未阐明。我们在这里报道，在洋地黄素通透性的细胞中，导入素α能够携带CaMKIV进入细胞核，而不需要导入素β或任何其他可溶性蛋白。Importinα的Importinβ结合缺陷突变体(DeltaIBB)也将CaMKIV携带到细胞核中，这强烈表明CaMKIV是以Importinβ非依赖的方式运输的。虽然CaMKIV直接与Importinα的C末端区域相互作用，但CaMKIV/Importinα复合体并不与Importinβ形成三元复合体，这解释了Importinβ对CaMKIV的核转运不是必需的。胞质内微量注射Importinα-DeltaIBB可提高CaMKIV的体内核转移率。这是第一个明确证明哺乳动物Importinα只携带一种货物蛋白进入细胞核的报告，而不使用经典的Importinβ依赖的运输系统。
Ca(2+)/calmodulin-dependent protein kinase type IV (CaMKIV) plays an essential role in the transcriptional activation of cAMP response element-binding protein-mediated signaling pathways. Although CaMKIV is localized predominantly in the nucleus, the molecular mechanism of the nuclear import of CaMKIV has not been elucidated. We report here that importin alpha is able to carry CaMKIV into the nucleus without the need for importin beta or any other soluble proteins in digitonin-permeabilized cells. An importin beta binding-deficient mutant (DeltaIBB) of importin alpha also carried CaMKIV into the nucleus, which strongly suggests that CaMKIV is transported in an importin beta-independent manner. While CaMKIV directly interacted with the C-terminal region of importin alpha, the CaMKIV/importin alpha complex did not form a ternary complex with importin beta, which explains the nonrequirement of importin beta for the nuclear transport of CaMKIV. The cytoplasmic microinjection of importin alpha-DeltaIBB enhanced the rate of nuclear translocation of CaMKIV in vivo. This is the first report to demonstrate definitely that mammalian importin alpha solely carries a cargo protein into the nucleus without utilizing the classical importin beta-dependent transport system.