Aoyama Naoki, Oka Asako, Kitayama Kumiko, Kurumizaka Hitoshi, Harata Masahiko
Laboratory of Molecular Biology, Graduate School of Agricultural Science, Tohoku University, Tsutsumidori-Amamiyamachi 1-1, Aoba-ku, Sendai 981-8555, Japan.
Exp Cell Res. 2008 Feb 15;314(4):859-68. doi: 10.1016/j.yexcr.2007.11.020. Epub 2007 Dec 4.
The actin family consists of conventional actin and various actin-related proteins (Arps). Some of these Arps are localized in the nucleus, and a fraction of each of these nuclear Arps is functionally involved in chromatin remodeling and histone acetyltransferase complexes. On the other hand, in mitotic cells, the localization and function of the nuclear Arps are largely unknown. Human Arp8 (hArp8), an ortholog of yeast nuclear Arp8, was recently found to be associated with the hINO80-chromatin remodeling complex along with hArp5. Here we report that hArp8, but not hArp5, accumulates on mitotic chromosomes. This is the first example where a member of the actin family is found to be associated with mitotic chromosomes. Expression of truncated hArp8 proteins and depletion of endogenous hArp8 by RNA interference caused misalignment of mitotic chromosomes, suggesting that chromosome-associated hArp8 has a role in chromosome behavior. In contrast, depletion of hIno80 and hArp5 did not cause misalignment of chromosomes, suggesting that the role of hArp8 at mitotic chromosomes is independent of the activity of hINO80 complexes. These findings provide the first insight into a novel function of actin family members in mitosis.
肌动蛋白家族由传统肌动蛋白和各种肌动蛋白相关蛋白(Arps)组成。其中一些Arps定位于细胞核,并且这些核Arps中的每一种的一部分在功能上参与染色质重塑和组蛋白乙酰转移酶复合物。另一方面,在有丝分裂细胞中,核Arps的定位和功能在很大程度上是未知的。人Arp8(hArp8)是酵母核Arp8的直系同源物,最近发现它与hArp5一起与hINO80 - 染色质重塑复合物相关联。在这里我们报告hArp8而不是hArp5在有丝分裂染色体上积累。这是首次发现肌动蛋白家族成员与有丝分裂染色体相关联的例子。截短的hArp8蛋白的表达以及通过RNA干扰耗尽内源性hArp8导致有丝分裂染色体排列错误,这表明与染色体相关的hArp8在染色体行为中起作用。相反,耗尽hIno80和hArp5不会导致染色体排列错误,这表明hArp8在有丝分裂染色体上的作用独立于hINO80复合物的活性。这些发现首次揭示了肌动蛋白家族成员在有丝分裂中的新功能。