Gladfelter Amy S, Zyla Trevin R, Lew Daniel J
Department of Pharmacology and Cancer Biology, Box 3813, Duke University Medical Center, Durham, NC 27710, USA.
Eukaryot Cell. 2004 Aug;3(4):847-54. doi: 10.1128/EC.3.4.847-854.2004.
Septins form a cortical scaffold at the yeast mother-bud neck that restricts the diffusion of cortical proteins between the mother and bud and serves as a signaling center that is important for governing various cell functions. After cell cycle commitment in late G(1), septins are assembled into a narrow ring at the future bud site, which spreads to form a mature septin hourglass immediately after bud emergence. Although several septin regulators have been identified, it is unclear how they cooperate to assemble the septin scaffold. We have examined septin localization in isogenic strains containing single or multiple mutations in eight septin organization genes (CDC42, RGA1, RGA2, BEM3, CLA4, GIN4, NAP1, and ELM1). Our results suggest that these regulators act largely in parallel to promote either the initial assembly of the septin ring (CDC42, RGA1, RGA2, BEM3, and CLA4) or the conversion of the ring to a stable hourglass structure at the neck (GIN4, NAP1, and ELM1). Aberrant septin localization patterns in mutant strains could be divided into apparently discrete categories, but individual strains displayed heterogeneous defects, and there was no clear-cut correspondence between the specific mutations and specific categories of defect. These findings suggest that when they are deprived of their normal regulators, septin scaffolds collapse into a limited repertoire of aberrant states in which the nature of the mutant regulators influences the probability of a given aberrant state.
Septin蛋白在酵母母细胞与芽体的颈部形成一个皮质支架,该支架限制了皮质蛋白在母细胞和芽体之间的扩散,并作为一个信号中心,对调控各种细胞功能至关重要。在G(1)晚期细胞周期进入承诺期后,Septin蛋白在未来的芽体部位组装成一个狭窄的环,芽体出现后立即扩展形成成熟的Septin沙漏结构。尽管已经鉴定出几种Septin调节因子,但尚不清楚它们如何协同组装Septin支架。我们研究了在八个Septin组织基因(CDC42、RGA1、RGA2、BEM3、CLA4、GIN4、NAP1和ELM1)中含有单个或多个突变的同基因菌株中Septin的定位。我们的结果表明,这些调节因子在很大程度上并行发挥作用,以促进Septin环的初始组装(CDC42、RGA1、RGA2、BEM3和CLA4)或在颈部将环转化为稳定的沙漏结构(GIN4、NAP1和ELM1)。突变菌株中异常的Septin定位模式可分为明显不同的类别,但个别菌株表现出异质性缺陷,并且特定突变与特定缺陷类别之间没有明确的对应关系。这些发现表明,当Septin支架失去其正常调节因子时,它们会坍缩成有限的异常状态集合,其中突变调节因子的性质会影响给定异常状态的概率。