Fhos2, a novel formin-related actin-organizing protein, probably associates with the nestin intermediate filament
Fhos2, a novel formin-related actin-organizing protein, probably associates with the nestin intermediate filament
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DOI：
10.1111/j.1365-2443.2005.00867.x
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发表时间：
2005-07-01
期刊：
影响因子：
2.1
通讯作者：
Sumimoto, H
中科院分区：
文献类型：
--
作者：
Kanaya, H;Takeya, R;Sumimoto, H
Fhos 1是哺乳动物形成蛋白家族的蛋白质，并且作为肌动蛋白微丝的组织者起作用。在这里，我们克隆了一种新的Fhos同系物，命名为Fhos 2的人类和小鼠cDNA。Fhos 2的信息在心脏、肾脏和大脑中表达，而这些地方Fhos 1 mRNA并不丰富。Fhos 2的两种剪接变体以组织特异性方式存在;较长的变体Fhos 2L是心脏中的主要形式，而肾脏和大脑主要表达编码较短蛋白质的Fhos 2S。两个Fhos 2变体的活性形式以及Fhos 1的过表达诱导HeLa细胞中肌动蛋白应力纤维的形成，表明Fhos 2充当肌动蛋白组织蛋白。使用大鼠成心肌细胞H9 c2（2-1）细胞的生化分析表明，内源性Fhos 2富集在中间丝部分。与此一致，Fhos 2定位于巢蛋白中间丝，但不定位于其他细胞骨架，如用抗Fhos 2抗体对H9 c2（2-1）细胞染色所证明的。此外，Fhos 2存在于胎鼠脑的表达巢蛋白的神经上皮细胞中。因此，Fhos 2不仅具有肌动蛋白组织活性，而且还与巢蛋白结合，这可能意味着Fhos 2介导的巢蛋白中间丝和肌动蛋白微丝之间的联系。
Fhos1 is a mammalian formin-family protein, and functions as an organizer of the actin microfilament. Here we have cloned human and mouse cDNAs for a novel Fhos homolog, designated Fhos2. The messages for Fhos2 are expressed in the heart, kidney, and brain, where the Fhos1 mRNAs are not abundant. Two splice variants of Fhos2 exist in a tissue-specific manner; the longer variant Fhos2L is the major form in the heart, whereas the kidney and brain predominantly express Fhos2S that encodes a shorter protein. Over-expression of an active form of the two Fhos2 variants, as well as that of Fhos1, induces the formation of actin stress fibers in HeLa cells, suggesting that Fhos2 acts as an actin-organizing protein. Biochemical analysis using rat cardiomyoblastic H9c2 (2-1) cells reveals that endogenous Fhos2 is enriched in the intermediate filament fraction. Consistent with this, Fhos2 localizes to the nestin intermediate filament but not to other cytoskeletons, as demonstrated by staining of H9c2 (2-1) cells with anti-Fhos2 antibodies. Furthermore, Fhos2 is present in nestin-expressing neuroepithelial cells of the fetal rat brain. Thus, Fhos2 not only has the actin-organizing activity but also associates with nestin, which may imply a Fhos2-mediated link between the nestin intermediate filament and actin microfilament.