The design principles underlying cell polarity in yeast

描述（由申请人提供）： 建立空间组织是所有生命系统的基本要求。细胞组织中的一个关键因素是细胞极性-存在一个控制过程，如结构组装，细胞器运输和大分子定位的定向轴。细胞极性是几乎所有细胞类型和各种生理过程所必需的，如细胞分化、细胞运动、神经元生长和免疫反应。 在芽殖酵母Saccharomyces cerevisiae的生命周期中，细胞极性对于交配和芽的形成至关重要。Rho家族的GTdCdc 42是细胞极化的关键调节因子和读出器，并且极化需要在质膜上的特定位点处积累活性Cdc 42。极化通常发生在响应空间和时间线索。然而，在不存在不对称诱导信号的情况下，酵母细胞仍然具有自发地降解的能力，尽管是在随机方向上。我们假设，细胞极性是通过两个过程的耦合：识别不对称的线索，并激活一个内在的，自发的机制，打破对称。 这项调查的首要目标是解剖，解开，并重新组装在酵母芽殖途径的极化机制。我们的方法利用了数学建模和酵母分子遗传学的综合优势。本研究的目的有三：前两个目的是研究Cdc 42自发极化的两种机制，一种依赖于细胞骨架，另一种独立于细胞骨架。第三个目的是研究如何定位信号，放大通过GTdR级联，偏置这些自发的极化机制，产生一个单一的，强大的，指定的网站Cdc 42极化。

DESCRIPTION (provided by applicant): Establishing spatial organization is a fundamental requirement for all living systems. A critical element in cellular organization is cell polarity - the presence of a directed axis that controls processes such as structural assembly, organelle transport, and localization of macromolecules. Cell polarity is required for nearly all cell types and for diverse physiological processes, such as cell differentiation, cell motility, neuronal growth, and immune responses. In the life cycle of the budding yeast Saccharomyces cerevisiae, cell polarity is critical for mating and bud formation. The Rho-family GTPase Cdc42 is a key regulator and readout of cell polarization and accumulation of activeCdc42 at specific sites on the plasma membrane is required for polarization. Polarization normally occurs in response to spatial and temporal cues. However, in the absence of asymmetric inductive signals, yeast cells still have the ability to spontaneously polarize, albeit in random directions. We hypothesize that cell polarity is brought about through a coupling of two processes: recognition of asymmetric cues, and activation of an intrinsic, spontaneous mechanism to break symmetry. The overarching aim of this investigation is to dissect, disentangle, and reassemble mechanisms of polarization in the yeast budding pathway. Our approach takes advantage of the combined strength of mathematical modeling and molecular genetics in yeast. The proposed research has three goals: The first two investigate two mechanisms of spontaneous polarization of Cdc42, one dependent and the other independent of the cytoskeleton. The third aim examines how localization signals, amplified through a GTPase cascade, bias these spontaneous mechanisms of polarization to yield a single, robust, specified site of Cdc42 polarization.