Chytrid fungi and the functional specification of actin networks

项目摘要 哺乳动物细胞经常同时使用它们的肌动蛋白细胞骨架用于多种功能，包括细胞运动， 细胞内吞作用、囊泡运输以及建立和维持细胞极性。虽然他们的成就不同 任务，功能不同的肌动蛋白网络共享结构组件和监管机构，可以包括 聚合因子、聚合物聚合物和促进网络周转的蛋白质。这种分子 哺乳动物细胞的多任务处理使得确定细胞如何控制肌动蛋白功能的子集变得困难。在 相比之下，芽殖酵母和裂殖酵母具有高度简化的肌动蛋白网络， 肌动蛋白网络控制的简单模型。酵母和人类肌动蛋白网络之间的巨大差异， 然而，这使得理解肌动蛋白细胞骨架调节的哪些原则是共享的变得困难。壶菌 真菌代表了一个天然的桥梁之间的充分理解肌动蛋白网络的酵母和精心制作的肌动蛋白 有三个原因。首先，壶菌的进化地位福尔斯酵母和 人体细胞第二，它们保留了酵母失去的重要肌动蛋白调节因子， 肌动蛋白网络在复杂性上是中等的。第三，也是最重要的，壶菌经历了一个自然的 从类人爬行细胞到类酵母细胞的发育转变。因此我们用壶菌 真菌研究与人类健康相关的肌动蛋白网络的进化和规范。我们已经确定了一 大量与人类细胞中发现的肌动蛋白调节因子相似的壶菌肌动蛋白细胞骨架调节因子，以及 另外的真菌特异性肌动蛋白调节剂。我们最近还开发了控制从 类人至类酵母细胞，以及分子转化和外源基因的方法 表情我们将使用这些方法来确定控制动物样和酵母样的机制 肌动蛋白网络的壶菌和它们之间的发展过渡。这项工作将帮助我们确定 肌动蛋白调节系统如何引起发育过程中观察到的肌动蛋白网络的多样性 过渡和进化时间。

PROJECT SUMMARY Mammalian cells often use their actin cytoskeleton simultaneously for multiple functions, including cell motility, endocytosis, vesicular trafficking, and to establish and maintain cell polarity. Although they accomplish different tasks, functionally distinct actin networks share structural components and regulators that can include polymerization factors, polymer bundlers, and proteins that promote network turnover. This molecular multitasking by mammalian cells makes it difficult to determine how cells control subsets of actin functions. In contrast, budding and fission yeast have highly simplified actin networks that have been used to develop simple models of actin network control. The vast differences between yeast and human actin networks, howevxer, make it difficult to understand which principles of actin cytoskeletal regulation are shared. Chytrid fungi represent a natural bridge between the well-understood actin networks of yeast and the elaborate actin networks of human cells for three reasons. First, the evolutionary position of chytrids falls between yeast and human cells. Second, they have retained important actin regulators that have been lost by yeast, making their actin networks are intermediate in complexity. Third, and most importantly, chytrid fungi undergo a natural developmental transition from human-like crawling cells to a yeast-like cell type. We are therefore using chytrid fungi to study the evolution and specification of actin networks relevant to human health. We have identified a large number of chytrid actin cytoskeletal regulators similar to actin regulators found in human cells, as well as additional fungal-specific actin regulators. We have also recently developed methods to control the switch from the human-like to the yeast-like cells, as well as methods for molecular transformation and exogenous gene expression. We will use these approaches to determine the mechanisms that control animal-like and yeast-like actin networks in chytrids and the developmental transitions between them. This work will help us determine how actin regulatory systems give rise to the observed diversity of actin networks across developmental transitions and evolutionary time.