Non-endosomal roles of ESCRT-III in yeast

转运所需的内体分选复合体(ESCRT)蛋白参与了许多不同的细胞过程，如内体蛋白分选、HIV萌发、胞质分裂、质膜修复和有丝分裂期间核膜的重新密封。我们在这个项目中的主要目标是探索ESCRT-III在酵母中的新的非内体功能，重点是含有ESCRT-III复合体的Chm7。到目前为止，我们的结果表明Chm7作为ESCRT-III复合体的一部分在内质网发挥作用。目前尚不清楚是什么构成了这一功能。为了确定Chm7的功能，我们将探索关于酵母Chm7的内质网功能的合理假设。这些假说借鉴了其他研究小组的发现，特别是最近关于CHMP7的发现，CHMP7是酵母Chm7的哺乳动物同源基因。我们将特别关注Chm7在核孔监测、核膜完整性和内质网重塑中的潜在作用。我们将从Chm7的膜结合、Chm7复合体的组成以及它与Vps4的相互作用方面进一步表征Chm7。此外，我们还将启动Mos10/Vps60复合体的功能研究。Mos10是一种孤立的ESCRT-III蛋白；到目前为止，该蛋白的功能尚不清楚。

Endosomal sorting complex required for transport (ESCRT) proteins are involved in many different cellular processes, like endosomal protein sorting, HIV-budding, cytokinesis, plasma membrane repair and resealing of the nuclear envelope during mitosis. Our main goal in this project is to explore new, non-endosomal functions of ESCRT-III in yeast with the focus on the Chm7 containing ESCRT-III complex. Our results so far suggest that Chm7 plays a role at the endoplasmic reticulum as part of an alternative ESCRT-III complex. What constitutes this function is at present unknown. To identify the Chm7 function, we will explore plausible hypotheses about the putative ER function of yeast Chm7. These hypotheses draw upon findings by other groups, especially the recent findings on CHMP7, the mammalian orthologue of yeast Chm7. We will especially focus on potential roles of Chm7 in nuclear pore surveillance, nuclear envelope integrity and ER remodeling. We will further characterize Chm7 with respect to its membrane association, the composition of the Chm7 complex and its interaction with Vps4. Furthermore, we will initiate a functional study of the Mos10/Vps60 complex. Mos10 is an orphan ESCRT-III protein; no clear function could be attributed to this protein so far.