The secretory pathway is remodeled during the differentiation of epithelial cells to form cyst and tubules. It is known that Golgi apparatus relocates to the apical side in front of the nucleus during the polarization of epithelial cells. Similarly, it is also known that Golgi apparatus, which is situated at the center of the secretory pathway, relocates to the front side of the moving cells. We have been reported that this relocation of the Golgi apparatus is dependent on the phosphorylation of GRASP65, a Golgi matrix protein. On the other hand, it was recently reported that some proteins could be secreted in a polarized fashion depending on GRASP65 but bypassing the Golgi apparatus. Under these circumstances, we are trying to understand how the secretory transport pathway, especially traffic trough the Golgi apparatus, is remodeled during the cyst and tubule formation using cultured cells and zebrafish.

We are going to conduct research from three aspects using developmental, cell biological and molecular biological techniques. (1) The mechanism of GRASP65 phosphorylation in relation to the relocation of the Golgi apparatus is analyzed. The mechanism of GRASP65 redirection to the plasma membrane is also analyzed. (2) Contribution of the remodeling of the secretory pathway for cell polarization and epithelial tubule formation is evaluated using MDCK and 16HBE14o- as model systems. (3) The importance of the remodeling of secretory pathway in gastrulation, neural tube formation and vasculogenesis are explored using zebrafish as a model organism.

We have been studying the molecular mechanism of Golgi morphogenesis and remodeling. The significance of our research project lies in the extension of our research in collaboration with of researchers under this research grant. The understanding of the role of Golgi bypass pathway and the molecular mechanism of the Golgi remodeling will give insights for the understanding the mechanism of epithelial tubulogenesis and also for the underlying cell cycle and cell growth control mechanisms. Furthermore, the obtained knowledge will lead us to find targets for the manipulation of the tubulogenesis and new methods for the treatments of tubule related disease, such as cancer.