A systematic analysis of the regulation of small G proteins on the Golgi apparatus

• Applicant: Dr. Falko Riedel
• Subject Area: Cell Biology
• Term: from 2011 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 200496715

The Golgi apparatus is the central sorting station of the secretory pathway and the key connection to the endosomal system. The diversity of vesicular transport routes at the Golgi is regulated by the Arf and Rab families of small G proteins each of which localizes to a subset of Golgi membranes. The localization of these G proteins is controlled by specific regulators that either activate G proteins to induce translocation from the cytosol to a specific membrane or inactivate G proteins and cause release back to the cytosol. Various regulator families have been described and they are also peripherally associated with specific membranes. Interestingly, recent evidence has indicated that a G protein can control the localization of a second G protein by interacting with a regulator of that second G protein. Such cascades could couple organelle identity to temporal events as organelles mature, but the relationship of only a few G proteins has been studied to date.We aim to perform a systematic investigation of the regulation of all Rabs and Arfs that localize to the Golgi of Drosophila cultured cells. The insect Golgi is similar to its mammalian counterpart but genes in Drosophila tend to have fewer paralogs than in mammals, thus facilitating systematic studies. We will select all the Drosophila Rabs and Arfs and their known regulators that localize to the Golgi and study systematically their relationship. First, we will examine the localization of each protein upon RNA interference mediated knock-down of individual G proteins. Second, we will test for direct interactions between individual immobilized G proteins and each regulator. The data will be integrated into a network that we expect to explain how G proteins are regulated at the Golgi and account for the accuracy of transport processes that take place at this organelle. The network will be validated by relocating regulators to other organelles and by testing if the findings are conserved in mammalian cells.

• DFG Programme: Research Fellowships
• International Connection: United Kingdom
• Host: Professor Dr. Sean Munro