Signaling at the secretory pathway: implications for trafficking, cell polarity and metastasis

• Applicant: Privatdozent Dr. Gunter Schmidtke, since 8/2016
• Subject Area: Cell Biology
• Term: from 2010 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 195739672

There is currently little mechanistic insight into the role of the Golgi in polarity. In our previous work we showed that the Golgi matrix protein GM130 interacts with RasGRF2 and we show that all effects of GM130 on polarity were contingent on the interaction with RasGRF2. We also performed two screens addressing signaling at the Golgi. In a RNAi screen we identify PLCgamma-1 as a regulator of endoplasmic reticulum (ER) to Golgi trafficking. In a proteomic screen we found that the phosphorylation of Rab8A is differentially regulated by ERK1/2 and p38 MAPK. Finally, we also characterized the pseudophosphatase STYX as a regulator of ERK1/2 signaling, directional cell migration, Golgi architecture and of cell fate decisions. In the current application we will investigate the following questions:(I) Role of GM130 in the regulation of polarity in vivo(II) Role of GM130 in the regulation of invasion and metastasis formation. This will be studied using cell culture models as well as in-vivo model(III) Explore the possibility whether PLC-gamma1 is part of an autochthonous signaling cascade regulating the biogenesis of the intermediate compartment (ERGIC) and ER-Golgi trafficking(IV) Role of phosphorylation of Rab8A in the regulation of post-Golgi traffickingOur work will contribute to a better understanding of how signaling to and from endomembranes regulates organelle homeostasis, cell invasion and metastatic dissemination.

• DFG Programme: Research Grants
• Ehemaliger Antragsteller: Professor Dr. Hesso Farhan, until 7/2016