TEMPORAL DISSECTION OF AUTOPHAGOSOME FORMATION IN SACCHAROMYCES CEREVISIAE

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子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，理解自噬途径的中心部分，即自噬体形成过程至关重要。迄今为止，已经使用酵母模型系统鉴定了大约30个自噬相关（ATG）基因。其中，15个是从酵母到人类的保守基因，是自噬体形成所必需的;这些基因的产物被称为核心机器蛋白。据推测，这些核心机器蛋白在吞噬细胞组装位点（PAS）的功能。 PAS基本上是未表征的，即使它被认为在自噬体生物发生中起着重要作用。因此，有一些基本的问题，如该网站的膜性质，是否吞噬细胞扩大囊泡融合，以及是否Atg蛋白（几乎所有的都在很大程度上与PAS结合）在PAS的特定位置形成复合物，例如在吞噬细胞的生长端（注意，PAS和吞噬细胞之间的确切关系尚不清楚; PAS可能发育成吞噬细胞，或可能为对应于吞噬细胞的单独位点提供膜）。

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).