Stress-induced nucleocytoplasmic shuttling of TDP-43 is controlled by eIF-5A hypusination

Aggregation and phosphorylation of TAR DNA-binding protein-43, TDP-43, has been found to be associated with the neuropathology of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTLD). It has been proposed that TDP-43 accumulation in stress granules (SG) may contribute to the aggregation of TDP43. Eukaryotic translational initiation factor 5A (eIF5A) is hypusinated by deoxyhypusine synthase (DHS) and deoxyhypusine hydroxylase (DOHH). It is involved at the level of mRNA turnover, cell proliferation, and protein translational elongation. In this experiment we sought to determine the function of hypusinated eIF5a in relation to TDP-43 pathology in nuclear and cytoplasmic compartments under cellular stress.