Publikationsrepositorium - Helmholtz-Zentrum Dresden-Rossendorf

Already decades ago, we and many other groups showed a nucleo-cytoplasmic translocation of La protein in cultured cells. This shuttling of La protein was seen after e.g. UV irradiation, virus infections, hydrogen peroxide exposure, and Fenton reaction based on iron or copper ions. In common, all these conditions are somehow related to oxidative stress. Unfortunately, all these harsh conditions could also cause an artificial release of La protein. Even until today, the shut-tling and a cytoplasmic function of La/SS-B are controversially discussed. Moreover, the driving mechanism for the shuttling of La protein remains unclear. Recently we showed that La protein undergoes redox dependent conformational changes. Moreover, we developed anti-La mono-clonal antibodies (anti-La mAbs) which are specific for either the reduced form of La protein or the oxidized form. Using these tools, here we show that redox dependent conformational changes are the driving force for the shuttling of La protein. Moreover, we show that transloca-tion of La protein to the cytoplasm can be triggered in a ligand/receptor dependent manner un-der physiological conditions. We show that ligands of toll-like receptors lead to a redox de-pendent shuttling of La protein. The shuttling of La protein depends on the redox status of the respective cell type. Endothelial cells are usually resistant to the shuttling of La protein while dendritic cells are highly sensitive. However, deprivation of intracellular reducing agents in endothelial cells turns endothelial cells sensitive to a redox dependent shuttling of La protein.