O'Halloran T J, Spudich J A
Department of Cell Biology, Stanford University School of Medicine, CA 94305.
Proc Natl Acad Sci U S A. 1990 Oct;87(20):8110-4. doi: 10.1073/pnas.87.20.8110.
The study of engineered Dictyostelium mutants with altered or missing myosin has revealed the molecule to be essential both for cytokinesis and for completion of the complex Dictyostelium developmental cycle. To explore the biological role of the carboxyl-terminal portion of the myosin tail, we have created a Dictyostelium cell line bearing a mutation designated my delta C34 in the myosin (mhcA) locus. This cell line produces a truncated myosin protein lacking the 34-kDa carboxyl terminus of the wild-type tail. Southern blots of the mutant cells show that the myosin gene was disrupted by homologous recombination of the transforming plasmid into the myosin locus. Based on in vitro studies of myosin functional domains, the 200-kDa truncated myosin was designed to include a domain important for assembly but to eliminate a domain important for threonine phosphorylation. The mutant cells are defective in cytokinesis, similar to those mutants that are either devoid of myosin (null cells) or contain a truncated 140-kDa myosin (hmm cells). However, unlike previous mutants, the cells carrying the my delta C34 mutation are able to complete the Dictyostelium developmental cycle to form fruiting bodies. Thus a truncated 200-kDa myosin can substitute for native myosin to function in developing cells. These results demonstrate that the 34-kDa carboxyl terminus of myosin, which contributes regulated phosphorylation sites and 20% of the total length of the rod, is not required for the developmental cycle of Dictyostelium.
对肌球蛋白发生改变或缺失的盘基网柄菌工程突变体的研究表明,该分子对于胞质分裂以及完成复杂的盘基网柄菌发育周期均至关重要。为了探究肌球蛋白尾部羧基末端部分的生物学作用,我们构建了一个盘基网柄菌细胞系,该细胞系在肌球蛋白(mhcA)基因座上带有一个名为my delta C34的突变。这个细胞系产生一种截短的肌球蛋白蛋白,缺失野生型尾部的34 kDa羧基末端。突变细胞的Southern印迹显示,肌球蛋白基因因转化质粒与肌球蛋白基因座的同源重组而被破坏。基于对肌球蛋白功能结构域的体外研究,设计出的200 kDa截短肌球蛋白包含一个对组装重要的结构域,但去除了一个对苏氨酸磷酸化重要的结构域。突变细胞在胞质分裂方面存在缺陷,类似于那些要么缺乏肌球蛋白的突变体(缺失细胞),要么含有截短的140 kDa肌球蛋白的突变体(hmm细胞)。然而,与之前的突变体不同,携带my delta C34突变的细胞能够完成盘基网柄菌的发育周期以形成子实体。因此,截短的200 kDa肌球蛋白可以替代天然肌球蛋白在发育中的细胞中发挥作用。这些结果表明,肌球蛋白的34 kDa羧基末端,它贡献了调节性磷酸化位点以及杆状部分总长度的20%,对于盘基网柄菌的发育周期并非必需。