Our group focuses on signaling to and from the secretory pathway. The two major lines of investigation are:
The role of the Golgi in directional cell migration
The secretory pathway is composed of the rough endoplasmic reticulum (ER), the ER exit sites (ERES), the intermediate compartment (ERGIC), the Golgi apparatus and the various post Golgi compartments along the exocytic route. Organelles of the secretory pathway provide the proper environment for protein folding and post-translational modification. In addition, these cellular organelles also have other cellular functions, like the role of the Golgi apparatus in directional polarity. Upon induction of directional cell movement, the Golgi polarizes towards the leading edge. Any interference with the structural integrity of the Golgi apparatus, will result in an inhibition of directional cell migration. In our previous work, we identified 38 kinases and phosphatases (so called Golgi-class hits) that regulated the structural integrity of the Golgi. Knockdown of Golgi-class hits also inhibits directional migration as well as orientation of the Golgi towards the leading edge (Farhan et al, 2010).
Wound-scratch assay. HeLa cells were transfected with siRNA as indicated. After 72 h, a scratch was introduced in cell monolayer. Cells were fixed after 5 h (upper row) and stained for Giantin (Golgi marker) to visualize Golgi orientation towards the wound (white line).Cells were also fixed after 24 h (lower row) and stained with conA (to label the entire cell) and wound closure was determined. Note that knockdown of AKAP28 fragments the Golgi and inhibits its orientation towards the leading edge, which results in an inhibition of wound closure on the next day.
Mutual regulation between the secretory pathway and cellular signaling cascades
In recent years it has become increasingly appreciated that endomembranes constitute hubs for signaling molecules (Farhan & Rabouille, 2011). However, it remains unclear to what extent, for instance the presence of a Golgi ribbon, is involved in signal propagation through the MAPK pathway. By disrupting the morpho-functional organization of the secretory pathway in combination of modeling approaches (anchored networks and modeling signaling pathways), we hope to gain a deeper insight into spatial regulation of MAPK pathways.
| Biotechnology Institute Thurgau |
| at the University of Constance |
| Unterseestrasse 47 |
| CH-8280 Kreuzlingen |
| Switzerland |
| Fon +41 (0)71 678 5020 |
| Fax +41 (0)71 678 5021 |
