Fig. 8: Schematic view of the link between phosphorylation of the C-terminal domain of TDP-43 and its sub-cellular location in cells.
From: TDP-43 nuclear retention is antagonized by hypo-phosphorylation of its C-terminus in the cytoplasm
According to our results, the dephosphorylated state of TDP-43 promotes its cytoplasmic retention with cytoplasmic condensates as observed in the case of 18A mutant or in the presence of protein kinase inhibitors. Indeed, the hypo-phosphorylation of TDP-43 in the cytoplasm positively regulates protein-protein interaction, which antagonizes the import of cytoplasmic TDP-43 to the nucleus leading to TDP-43 nuclear depletion and its retention in the cytoplasm. In contrast, as observed for 18E mutant as well as in the presence of protein phosphatase inhibitors, phosphorylated TDP-43 is enriched in the nucleus.
