Hill K L, Catlett N L, Weisman L S
Department of Biochemistry, University of Iowa, Iowa City 52242, USA.
J Cell Biol. 1996 Dec;135(6 Pt 1):1535-49. doi: 10.1083/jcb.135.6.1535.
During cell division, cytoplasmic organelles are not synthesized de novo, rather they are replicated and partitioned between daughter cells. Partitioning of the vacuole in the budding yeast Saccharomyces cerevisiae is coordinated with the cell cycle and involves a dramatic translocation of a portion of the parental organelle from the mother cell into the bud. While the molecular mechanisms that mediate this event are unknown, the vacuole's rapid and directed movements suggest cytoskeleton involvement. To identify cytoskeletal components that function in this process, vacuole inheritance was examined in a collection of actin mutants. Six strains were identified as being defective in vacuole inheritance. Tetrad analysis verified that the defect cosegregates with the mutant actin gene. One strain with a deletion in a myosin-binding region was analyzed further. The vacuole inheritance defect in this strain appears to result from the loss of a specific actin function; the actin cytoskeleton is intact and protein targeting to the vacuole is normal. Consistent with these findings, a mutation in the actin-binding domain of Myo2p, a class V unconventional myosin, abolishes vacuole inheritance. This suggests that Myo2p serves as a molecular motor for vacuole transport along actin filaments. The location of actin and Myo2p relative to the vacuole membrane is consistent with this model. Additional studies suggest that the actin filaments used for vacuole transport are dynamic, and that profilin plays a critical role in regulating their assembly. These results present the first demonstration that specific cytoskeletal proteins function in vacuole inheritance.
在细胞分裂过程中,细胞质细胞器并非重新合成,而是进行复制并在子细胞间分配。出芽酵母酿酒酵母中液泡的分配与细胞周期协调一致,涉及亲代细胞器的一部分从母细胞向芽的剧烈转运。虽然介导这一过程的分子机制尚不清楚,但液泡快速且定向的移动表明细胞骨架参与其中。为了鉴定在此过程中发挥作用的细胞骨架成分,对一组肌动蛋白突变体的液泡遗传进行了研究。鉴定出六个菌株在液泡遗传方面存在缺陷。四分体分析证实该缺陷与突变的肌动蛋白基因共分离。对一个肌球蛋白结合区域缺失的菌株进行了进一步分析。该菌株中液泡遗传缺陷似乎是由于特定肌动蛋白功能丧失所致;肌动蛋白细胞骨架完整,且蛋白质靶向液泡正常。与这些发现一致,V类非常规肌球蛋白Myo2p的肌动蛋白结合结构域发生突变会消除液泡遗传。这表明Myo2p作为分子马达,沿着肌动蛋白丝进行液泡运输。肌动蛋白和Myo2p相对于液泡膜的位置与该模型一致。进一步的研究表明,用于液泡运输的肌动蛋白丝是动态的,并且肌动蛋白单体结合蛋白在调节其组装中起关键作用。这些结果首次证明了特定的细胞骨架蛋白在液泡遗传中发挥作用。