Figure 7

Schematic diagram of the retrograde trafficking of β-DG from the cell surface to the nucleus. (1) DG is synthesized in the ER as a precursor that undergoes a proteolytic cleavage to generate two subunits: α- and β-DG. (2) α-DG and β-DG maintain a non-covalent interaction and are transported from the ER to the Golgi apparatus, where both proteins are glycosylated (3) and then transported to the PM, where they interact with the DAPC (4). (5) β-DG is endocytosed from the PM, a process positively modulated by its phosphorylation on Tyr⁸⁹⁰. (7) β-DG is further translocated from the PM to the ER, and based on the β-DG-Sec61β interaction, it is likely that the Sec61 translocon releases β-DG from the ER membrane, prior to be recognized by the importin system to enter the nucleus through the NPC (8A-9). As both β-DG and Sec61 have been found in the NE, an alternative possibility is that β-DG moves from the ER to the NE by lateral diffusion to interact there with Sec61 to be directly delivered to the nucleoplasm (8B-9). Another alternative route for nuclear translocation is that β-DG-containing endosomes fuse directly to the nuclear membrane to discharge their contents in the nuclear envelope so that β-DG gets further translocated into the nucleoplasm (7B).