Li Shihe, Oakley C Elizabeth, Chen Guifang, Han Xiaoyan, Oakley Berl R, Xiang Xin
Department of Biochemistry and Molecular Biology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Mol Biol Cell. 2005 Aug;16(8):3591-605. doi: 10.1091/mbc.e04-12-1071. Epub 2005 Jun 1.
In Aspergillus nidulans, cytoplasmic dynein and NUDF/LIS1 are found at the spindle poles during mitosis, but they seem to be targeted to this location via different mechanisms. The spindle pole localization of cytoplasmic dynein requires the function of the anaphase-promoting complex (APC), whereas that of NUDF does not. Moreover, although NUDF's localization to the spindle poles does not require a fully functional dynein motor, the function of NUDF is important for cytoplasmic dynein's targeting to the spindle poles. Interestingly, a gamma-tubulin mutation, mipAR63, nearly eliminates the localization of cytoplasmic dynein to the spindle poles, but it has no apparent effect on NUDF's spindle pole localization. Live cell analysis of the mipAR63 mutant revealed a defect in chromosome separation accompanied by unscheduled spindle elongation before the completion of anaphase A, suggesting that gamma-tubulin may recruit regulatory proteins to the spindle poles for mitotic progression. In A. nidulans, dynein is not apparently required for mitotic progression. In the presence of a low amount of benomyl, a microtubule-depolymerizing agent, however, a dynein mutant diploid strain exhibits a more pronounced chromosome loss phenotype than the control, indicating that cytoplasmic dynein plays a role in chromosome segregation.
在构巢曲霉中,有丝分裂期间胞质动力蛋白和NUDF/LIS1定位于纺锤体极,但它们似乎是通过不同机制靶向该位置的。胞质动力蛋白的纺锤体极定位需要后期促进复合体(APC)的功能,而NUDF则不需要。此外,虽然NUDF定位于纺锤体极不需要完全功能性的动力蛋白马达,但NUDF的功能对于胞质动力蛋白靶向纺锤体极很重要。有趣的是,γ-微管蛋白突变体mipAR63几乎消除了胞质动力蛋白在纺锤体极的定位,但对NUDF在纺锤体极的定位没有明显影响。对mipAR63突变体的活细胞分析显示,在后期A完成之前,染色体分离存在缺陷,并伴有纺锤体意外伸长,这表明γ-微管蛋白可能将调节蛋白招募到纺锤体极以促进有丝分裂进程。在构巢曲霉中,有丝分裂进程显然不需要动力蛋白。然而,在存在少量微管解聚剂苯菌灵的情况下,动力蛋白突变体二倍体菌株比对照表现出更明显的染色体丢失表型,这表明胞质动力蛋白在染色体分离中起作用。