Defining the cellular architecture: intrinsic regulation of organelle size, shape and number

真核细胞尽管有膜在分泌和内吞系统中不断流动（或运输），但仍保持其结构。细胞器成熟是内吞系统运输的基础，需要膜融合、裂变和内陷事件。这些过程必须平衡以保持细胞器的大小、形状和数量；定义细胞结构并允许适当的细胞器功能和继承的属性。虽然目前还不清楚这种平衡是如何实现的，但我们知道，发挥作用的机制是系统的内在因素。此外，管腔体积对这种平衡很重要，因为体积的变化会触发Rab GTPase信号传导，从而控制细胞器形态。然而，与细胞体积不同，控制细胞器体积的机制尚不清楚。本提案的目的是确定和表征控制细胞器体积和调节Rab信号传导以维持细胞器大小，形状和数量的机制。为了实现这一目标，我将以酿酒葡萄球菌及其液泡为模型，对细胞器融合、裂变和内陷进行定量分析，同时对管腔体积和离子进行测量。这项工作将代表细胞生物学领域的重大突破，并对我们对细胞内运输和真核细胞结构如何定义和维持的基本理解具有全球意义。

The eukaryotic cell maintains its architecture despite the continuous flow (or trafficking) of membrane through the secretory and endocytic systems. Organelle maturation underlies trafficking in the endocytic system, and requires membrane fusion, fission and invagination events. These processes must be balanced to maintain organelle size, shape and number; properties that define the architecture of the cell and permit proper organelle function and inheritance. Although it is unclear how this balance is achieved, we know that mechanisms in play are intrinsic to the system. Furthermore lumenal volume is important for this balance, as changes in volume trigger Rab GTPase signaling, which in turn controls organelle morphology. Unlike cellular volume however, the mechanisms that control organelle volume are poorly understood. The aim of this proposal is to identify and characterize mechanisms that control organelle volume and regulate Rab signaling to maintain organelle size, shape and number. To achieve this goal, I will perform quantitative assays of organelle fusion, fission and invagination in tandem with lumenal volume and ion measurements using S. cerevisiae and its vacuole as models. This work will represent a major breakthrough in the field of cell biology, and has global significance to our basic understanding of intracellular trafficking and how the eukaryotic cell architecture is defined and maintained.