ALS-Linked Mutant SOD1 Associates with TIA-1 and Alters Stress Granule Dynamics.

ALS-Linked Mutant SOD1 Associates with TIA-1 and Alters Stress Granule Dynamics. Neurochem Res. 2020 Oct 06;: Authors: Lee DY, Jeon GS, Sung JJ Abstract Amyotrophic lateral sclerosis (ALS) is a degenerative disorder caused by motor neuron loss. T-cell intracellular antigen-1 (TIA-1), a cytotoxic T lymphocyte granule-associated RNA binding protein, is a key component of stress granules. However, it remains uncertain whether ALS-causing superoxide dismutase-1 (SOD1) toxicity alters the dynamics of stress granules. Thus, through mouse and cell line models, and human cells and tissues, we showed the subcellular location of TIA-1 and its recruitment by stress granules following mutant SOD1-related stimuli. An overexpression of MTSOD1 resulted in increased TIA-1-positive cytoplasmic inclusions in the spinal cord tissue of SOD1G93A transgenic mouse and the SOD1G86S familial ALS patient. Moreover, we demonstrated the stages of ALS-like disease-dependent increase in TIA-1 in the spinal cord of transgenic mice. A similar increase of TIA-1 was found in the spinal cord of the SOD1G86S patient and induced pluripotent stem cell-derived neural stem cells from the SOD1G17S patient. By using immunoprecipitation assays in wild type (WT) human SOD1 (hSOD1) or mutant (MT) hSOD1-transfected motor neuronal cell lines and SOD1G93A transgenic mouse model, we observed that MTSOD1 interacts with TIA-1. In WT or MT hSOD1-transfected HEK293 and NSC-34 cells, th...
Source: Neurochemical Research - Category: Neuroscience Authors: Tags: Neurochem Res Source Type: research