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MIM.603518 2p13

Thursday 20 October 2005

T cell-restricted intracellular antigen-1 (TIA1)

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


- 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


- 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