TIA1

Definition: TIA1 is a 15-kD cytoplasmic granule-associated protein whose expression is restricted to CTLs and natural killer cells.

Pathology

 TIA1 Mutations in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Promote Phase Separation and Alter Stress Granule Dynamics.

• Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are age-related neurodegenerative disorders with shared genetic etiologies and overlapping clinical and pathological features.
• The study of a ALS/FTD family identified the P362L mutation in the low-complexity domain (LCD) of T cell-restricted intracellular antigen-1 (TIA1).
• Postmortem neuropathology of five TIA1 mutations carriers showed a consistent pathological signature with numerous round, hyaline, TAR DNA-binding protein 43 (TDP-43)-positive inclusions.
• TIA1 mutations significantly increased the propensity of TIA1 protein to undergo phase transition.
• In live cells, TIA1 mutations delayed stress granule (SG) disassembly and promoted the accumulation of non-dynamic SGs that harbored TDP-43.
• Moreover, TDP-43 in SGs became less mobile and insoluble.
• The identification of TIA1 mutations in ALS/FTD reinforces the importance of RNA metabolism and SG dynamics in ALS/FTD pathogenesis.
• PMID: 28817800 doi : 10.1016/j.neuron.2017.07.025

References

 Asano N, Suzuki R, Kagami Y, Ishida F, Kitamura K, Fukutani H, Morishima Y, Takeuchi K, Nakamura S. Clinicopathologic and Prognostic Significance of Cytotoxic Molecule Expression in Nodal Peripheral T-Cell Lymphoma, Unspecified. Am J Surg Pathol. 2005 Oct;29(10):1284-1293. PMID: 16160469