Stowers Institute for Medical Research, 1000 East 50(th) Street, Kansas City, MO 64110, USA.
Dev Cell. 2009 Dec;17(6):823-35. doi: 10.1016/j.devcel.2009.10.022.
In budding yeast, the highly conserved small GTPase Cdc42 localizes to the cortex at a cell pole and orchestrates the trafficking and deposition of cell surface materials required for building a bud or mating projection (shmoo). Using a combination of quantitative imaging and mathematical modeling, we elucidate mechanisms of dynamic recycling of Cdc42 that balance diffusion. Rdi1, a guanine nucleotide dissociation inhibitor (GDI), mediates a fast recycling pathway, while actin patch-mediated endocytosis accounts for a slower one. These recycling mechanisms are restricted to the same region of the nascent bud, as both are coupled to the Cdc42 GTPase cycle. We find that a single dynamic parameter, the rate of internalization inside the window of polarized delivery, is tuned to give rise to distinct shapes of Cdc42 distributions that correlate with distinct morphogenetic fates, such as the formation of a round bud or a pointed shmoo.
在出芽酵母中,高度保守的小分子 GTPase Cdc42 定位于细胞极的皮质,并协调细胞表面物质的运输和沉积,这些物质是构建芽或交配突起(shmoo)所必需的。我们使用定量成像和数学建模的组合,阐明了动态回收 Cdc42 的机制,这些机制平衡了扩散。GDI(鸟嘌呤核苷酸解离抑制剂)Rdi1 介导快速回收途径,而肌动蛋白斑块介导的内吞作用则是较慢的途径。这些回收机制仅限于新生芽的同一区域,因为它们都与 Cdc42 GTP 酶循环偶联。我们发现,单一动态参数,即极化输送窗内的内化速率,被调整为产生不同形状的 Cdc42 分布,这些分布与不同的形态发生命运相关,例如形成圆形芽或尖形 shmoo。