Geiser J R, Schott E J, Kingsbury T J, Cole N B, Totis L J, Bhattacharyya G, He L, Hoyt M A
Department of Biology, Johns Hopkins University, Baltimore, Maryland 21218, USA.
Mol Biol Cell. 1997 Jun;8(6):1035-50. doi: 10.1091/mbc.8.6.1035.
Kinesin-related Cin8p is the most important spindle-pole-separating motor in Saccharomyces cerevisiae but is not essential for cell viability. We identified 20 genes whose products are specifically required by cell deficient for Cin8p. All are associated with mitotic roles and represent at least four different functional pathways. These include genes whose products act in two spindle motor pathways that overlap in function with Cin8p, the kinesin-related Kip1p pathway and the cytoplasmic dynein pathway. In addition, genes required for mitotic spindle checkpoint function and for normal microtubule stability were recovered. Mutant alleles of eight genes caused phenotypes similar to dyn1 (encodes the dynein heavy chain), including a spindle-positioning defect. We provide evidence that the products of these genes function in concept with dynein. Among the dynein pathway gene products, we found homologues of the cytoplasmic dynein intermediate chain, the p150Glued subunit of the dynactin complex, and human LIS-1, required for normal brain development. These findings illustrate the complex cellular interactions exhibited by Cin8p, a member of a conserved spindle motor family.
驱动蛋白相关的Cin8p是酿酒酵母中最重要的纺锤极分离马达蛋白,但对细胞生存力并非必不可少。我们鉴定出20个基因,其产物是Cin8p缺陷细胞所特别需要的。所有这些基因都与有丝分裂作用相关,并且代表至少四种不同的功能途径。这些途径包括其产物作用于两条与Cin8p功能重叠的纺锤体马达途径的基因,即驱动蛋白相关的Kip1p途径和胞质动力蛋白途径。此外,还获得了有丝分裂纺锤体检查点功能和正常微管稳定性所需的基因。八个基因的突变等位基因导致了与dyn1(编码动力蛋白重链)相似的表型,包括纺锤体定位缺陷。我们提供的证据表明,这些基因的产物与动力蛋白协同发挥作用。在动力蛋白途径基因产物中,我们发现了胞质动力蛋白中间链、动力蛋白激活蛋白复合物的p150Glued亚基以及正常脑发育所需的人类LIS-1的同源物。这些发现说明了保守的纺锤体马达蛋白家族成员Cin8p所表现出的复杂细胞相互作用。