Knaus Michele, Wiget Philippe, Shimada Yukiko, Peter Matthias
Institute of Biochemistry, ETH Hönggerberg, Zürich, Switzerland.
Novartis Found Symp. 2005;269:47-54; discussion 54-8, 223-30.
Budding yeast serves as a powerful genetic model organism for studying the molecular mechanisms of cell polarity in single cells. Like other polarized eukaryotic cells, yeast cells possess polarity programs that regulate where they grow and divide. Establishment of a site of cell polarity may be conceptualized in several stages. First, cells mark a specific location at the cell surface for polarized cell growth and cell division. To define these sites, cells use intrinsic cues present in the cell or landmarks determined by extracellular signals such as morphogens. Second, these landmark proteins then recruit or activate polarity establishment proteins including small GTPases and their regulators. Positive and negative feedback mechanisms are required to transform these site-selection processes into a stable axis of polarity. Finally, these locally activated GTPase modules recruit and activate proteins that organize the actin cytoskeleton and cell growth. In this short review, we describe molecular pathways required to establish oriented cell polarity, and emphasize recent advances in defining positive and negative feedback mechanisms that together may translate an initially weak symmetry-breaking signal into a robust axis of polarity.
芽殖酵母是用于研究单细胞中细胞极性分子机制的强大遗传模式生物。与其他极化真核细胞一样,酵母细胞拥有调节其生长和分裂位置的极性程序。细胞极性位点的建立可分为几个阶段来理解。首先,细胞在细胞表面标记一个特定位置用于极化细胞生长和细胞分裂。为了定义这些位点,细胞利用细胞内存在的内在线索或由细胞外信号(如形态发生素)确定的地标。其次,这些地标蛋白随后招募或激活包括小GTP酶及其调节剂在内的极性建立蛋白。需要正反馈和负反馈机制将这些位点选择过程转化为稳定的极性轴。最后,这些局部激活的GTP酶模块招募并激活组织肌动蛋白细胞骨架和细胞生长的蛋白。在这篇简短的综述中,我们描述了建立定向细胞极性所需的分子途径,并强调了在定义正反馈和负反馈机制方面的最新进展,这些机制共同作用可能将最初微弱的对称性破坏信号转化为强大的极性轴。