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

细胞需要持续不断的营养供应，如氨基酸、脂质和离子。一个中央再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激酶复合物1（TORC 1）及其活化复合物，EGO/LamTOR复合物。除了与内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。在此资助的框架内，我的团队希望专注于酵母Rab 7-like GTp 4 Ypt 7在信号传导过程和液泡膜接触位点中的作用。我们最近发现了一个新的液泡-线粒体接触位点，称为vCLAMP，它是由HOPS亚基Vps 39和Ypt 7形成的。此外，我们的特点是IBAR蛋白Ivy 1作为一种新的Ypt 7效应器上的液泡，定位到液泡膜结构域，并影响液泡的生物发生。我们推测，Ypt 7功能的液泡是控制在不同的生长阶段的代谢活动的变化，并参与域的液泡形成。这些方面将在两个定义，vCLAMPs的细胞功能（项目1）和Ivy 1在控制液泡膜稳态（项目2）的功能平行项目。

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).