Role of the Rab GTPase Ypt7 in vacuole membrane contacts and signaling

细胞需要源源不断的营养物质，如氨基酸、脂质和离子。一个中心的循环细胞器是酵母溶酶体样空泡，它也是细胞生长的主要调节因子，TOR激酶复合体1(TORC1)及其激活复合体，EGO/LamTOR复合体。除了与内小体和其他囊泡的持续融合外，空泡还与其他细胞器形成接触部位，其功能仍然知之甚少。在这项资助的框架内，我的团队想要集中研究酵母Rab7样GTP酶Ypt7在液泡膜上的信号过程和接触部位中的作用。我们最近在一个新的空泡-线粒体接触位点上发现了vCLAMP，它由Hop亚单位Vps39和Ypt7组成。此外，我们还鉴定了Ibar蛋白IVy1是一种新的液泡Ypt7效应因子，定位于液泡膜域并影响液泡的发生。我们假设Ypt7在液泡上的功能在不同的生长阶段受代谢活性变化的控制，并参与液泡上区域的形成。这些方面将在两个明确的平行项目中讨论：vCLAMPs的细胞功能(项目1)和IVy1在控制液泡膜动态平衡中的功能(项目2)。

Cells require continuous supply of nutrients such as amino acids, lipids and ions. A central recycling organelle is the yeast lysosome-like vacuole, which also hosts a major regulator of cell growth, the TOR kinase complex 1 (TORC1) and its activating complex, the EGO/LamTOR complex. Apart from continuous fusion with endosomes and other vesicles, vacuoles form contact sites with other organelles, whose function is still poorly understood. Within the frame of this grant, my group would like to concentrate on the role of yeast Rab7-like GTPase Ypt7 in signaling processes and contact sites on the vacuole membrane. We recently identified on a novel vacuole-mitochondrial contacts site, called vCLAMP, which is formed by the HOPS subunit Vps39 and Ypt7. Furthermore, we characterized the IBAR protein Ivy1 as a novel Ypt7 effector on vacuoles that localizes to vacuolar membrane domains and affects vacuole biogenesis. We hypothesize that Ypt7 function on the vacuole is controlled during different growth phases on changes in metabolic activity and is involved domain formation on the vacuole. These aspects will be addressed in two defined, parallel projects on the cellular function of vCLAMPs (project 1) and the function of the Ivy1 in controlling vacuole membrane homeostasis (project 2).