TEMPORAL DISSECTION OF AUTOPHAGOSOME FORMATION IN SACCHAROMYCES CEREVISIAE

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 本项目的目标是充分探索自噬的生理功能。为此，了解自噬途径的中心部分，即自噬小体的形成过程是至关重要的。到目前为止，利用酵母模型系统已经鉴定了大约30个自噬相关(ATG)基因。其中15个基因从酵母到人类都是保守的，对自噬小体的形成是必不可少的；这些基因的产物被称为核心机械蛋白。据推测，这些核心机械蛋白在吞噬分子组装位置(PAS)起作用。 PAS基本上没有特征，尽管它被认为在自噬生物发生中发挥着基础作用。因此，有一些基本的问题，如这个部位的膜性质，噬菌体是否通过囊泡融合而膨胀，以及ATG蛋白(几乎所有的大部分都与PAS相关)是否以复合体的形式存在于PAS的特定位置，例如在噬菌体的生长端(请注意，PAS和噬菌体之间的确切关系尚不清楚；PAS可能发展为噬菌体，或者可能为与噬菌体对应的单独位置提供膜)。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The goal of this project is to fully explore the physiological functions of autophagy. For this, it is critical to understand the central part of the autophagy pathway, the autophagosome formation process. To date, approximately 30 autophagy-related (ATG) genes have been identified using yeast model systems. Among them, 15 are conserved from yeast to human and are essential for autophagosome formation; the products of these genes are termed the core machinery proteins. It was hypothesized that these core machinery proteins function at the phagophore assembly site (PAS). The PAS is essentially uncharacterized, even though it is thought to play a fundamental role in autophagosome biogenesis. Thus, there are basic questions such as the membrane nature of this site, whether the phagophore expands by vesicular fusion, and whether the Atg proteins (almost all of which associate in large part with the PAS) are in complexes at particular locations at the PAS, such as at the growing ends of the phagophore (note that the exact relationship between the PAS and the phagophore is not known; the PAS may develop into a phagophore, or may provide membrane to a separate site that corresponds to the phagophore).