| First Author | Lee S | Year | 2022 |
| Journal | Cells | Volume | 11 |
| Issue | 24 | PubMed ID | 36552734 |
| Mgi Jnum | J:333670 | Mgi Id | MGI:7411610 |
| Doi | 10.3390/cells11243972 | Citation | Lee S, et al. (2022) c-Abl Regulates the Pathological Deposition of TDP-43 via Tyrosine 43 Phosphorylation. Cells 11(24) |
| abstractText | Non-receptor tyrosine kinase, c-Abl plays a role in the pathogenesis of several neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. Here, we found that TDP-43, which was one of the main proteins comprising pathological deposits in amyotrophic lateral sclerosis (ALS), is a novel substrate for c-Abl. The phosphorylation of tyrosine 43 of TDP-43 by c-Abl led to increased TDP-43 levels in the cytoplasm and increased the formation of G3BP1-positive stress granules in SH-SY5Y cells. The kinase-dead mutant of c-Abl had no effect on the cytoplasmic localization of TDP-43. The expression of phosphor-mimetic mutant Y43E of TDP-43 in primary cortical neurons accumulated the neurite granule. Furthermore, the phosphorylation of TDP-43 at tyrosine 43 by c-Abl promoted the aggregation of TDP-43 and increased neuronal cell death in primary cortical neurons, but not in c-Abl-deficient primary cortical neurons. Identification of c-Abl as the kinase of TDP43 provides new insight into the pathogenesis of ALS. |
