Cell biological characterization of EBAG9/RCAS1 as a modifier of tumor-associated O-linked glycan expression
Final Report Abstract
Deposition of mature glycoconjugates at the plasma membrane of eukaryotic cells requires a coordinated topological and functional arrangement of the glycosylation machinery along the secretory pathway. A failure lo maintain such an order might be linked with the surface dexpression of truncated O-linked glycans, a hallmark of carcinomas which has been recognized for decades. While several genetic alterations could be associated with the generation of severely disturbed, cancer-associated glycan structures, among them loss or overexpression of glycosidases or glycan transferases, more complex traits of malignancy, including modulatory effects on the secretory pathway, have proven difficult to identify. Here, we idenlify a putative pathophysiological implication of EBAG9 for the secretory pathway in epithelial tumors. EBAG9 exhibits a dynamic inlracellular redistribution between ERGIC and cis-Golgi. The molecule colocalized wilh ERGIC markers, bul also with VSVG containing, COPI-positive transport carriers. Severe delay in transport of membrane glycoproteins from the ER to the cis-Golgi corresponded lo an interaction between EBAG9 and the COPI complex. Specific inhibition of the COPl-complex-dependent ER-Golgi trafficking route was proven by the relocalizalion of KDEL receptor and Mannosidase 11. EBAG9 imposed an expansion of vesicular-tubular clusters prior to their fusion with the cis-Golgi stacks. Thus, we have identified a novel pathogenetic principle, whereby interference of the estrogen-inducible tumor-associated antigen EBAG9 results in the occurrence of a tumor glycome in epithelial cancers.
Publications
- 2007. SorLA/LR11 regulates processing of amyloid precursor protein via interaction with adaptors GGA and PACS-1. J. Biol. Chem. 282, 32956-32964
Schmidt, V., A. Sporbert, M. Rohe, T. Reimer, A. Rehm, O.A. Andersen, and T.E. Willnow
- 2007. The UT-A1 urea transporter interacts with Snapin, a SNARE-associated protein. J. Biol. Chem. 282, 30097-30106
Mistry, A.C., R. Mallick, O. Fröhlich, J.D. Klein, A. Rehm, G. Chen, and J.M. Sands
