Chytrid fungi and the functional specification of actin networks

项目总结 哺乳动物细胞经常同时使用它们的肌动蛋白细胞骨架来实现多种功能，包括细胞运动， 内吞作用、囊泡运输，以及建立和维持细胞极性。尽管他们实现了不同的目标 任务、功能不同的肌动蛋白网络共享结构组件和调节器，这些组件和调节器可以包括 促进网络周转的聚合因子、聚合物束和蛋白质。这种分子 哺乳动物细胞的多任务处理使得很难确定细胞如何控制肌动蛋白的亚组功能。在……里面 相比之下，发芽酵母和分裂酵母具有高度简化的肌动蛋白网络，已被用来开发 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，这使得人们很难理解肌动蛋白细胞骨架调节的哪些原则是相同的。食蟹类 真菌是酵母肌动蛋白网络和精致肌动蛋白之间的天然桥梁。 人类细胞的网络有三个原因。首先，脊椎动物的进化位置介于酵母菌和 人类细胞。其次，他们保留了酵母失去的重要肌动蛋白调节器，使他们的 肌动蛋白网络的复杂性是中等的。第三，也是最重要的是，菊苣真菌经历了一种天然的 从类人爬行细胞向类酵母细胞类型的发育过渡。因此，我们使用chytrid 研究与人类健康相关的肌动蛋白网络的进化和规范。我们已经确定了一个 在人类细胞中发现了大量与肌动蛋白调控类似的chytrid肌动蛋白细胞骨架调节器，以及 额外的真菌特异性肌动蛋白调节剂。我们最近还开发了控制开关的方法 酵母样细胞的类人化，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类动物和类酵母的机制 卵裂中的肌动蛋白网络及其之间的发育转变。这项工作将帮助我们确定 肌动蛋白调控系统如何在发育过程中引起观察到的肌动蛋白网络的多样性 转变和进化时间。

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.