Liu-Yesucevitz L, Bilgutay A, Zhang YJ, Vanderweyde T, Vanderwyde T, Citro A, Mehta T, Zaarur N, McKee A, Bowser R, Sherman M, Petrucelli L, Wolozin B. Tar DNA binding protein-43 (TDP-43) associates with stress granules: analysis of cultured cells and pathological brain tissue. PLoS One. 2010;5(10):e13250. PubMed.
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This paper by Liqun Liu-Yesucevitz and colleagues is an important contribution in understanding the role that TDP-43 plays in human diseases such as ALS and FTLD. This is a solid publication that confirms previous studies that demonstrate TDP-43 is present in stress granules and that its localization to these granules is enhanced during cell stress (1,2). Additionally, they demonstrate that mutants of TDP-43 associated with ALS have increased stress granule formation both in the presence and absence of stressors. Strikingly, they show the accumulation of RIPA insoluble TDP-43 following arsenite treatment. This is also exacerbated in the disease-causing mutants. This is the first report of TDP-43 colocalization with stress granule proteins found in cytoplasmic inclusions from the brain and spinal cord of patients with FTLD and ALS.
Future studies will be needed to assess the importance and impact of stress granule proteins in the pathogenesis of these diseases and the mechanism by which TDP-43 is recruited to these granules. Additionally, this study raises the questions of what specific role TDP-43 plays in response to cellular stresses and whether TDP-43 is a bona fide stress response protein.
References:
Elvira G, Wasiak S, Blandford V, Tong XK, Serrano A, Fan X, del Rayo Sánchez-Carbente M, Servant F, Bell AW, Boismenu D, Lacaille JC, McPherson PS, DesGroseillers L, Sossin WS. Characterization of an RNA granule from developing brain. Mol Cell Proteomics. 2006 Apr;5(4):635-51. PubMed.
Moisse K, Volkening K, Leystra-Lantz C, Welch I, Hill T, Strong MJ. Divergent patterns of cytosolic TDP-43 and neuronal progranulin expression following axotomy: implications for TDP-43 in the physiological response to neuronal injury. Brain Res. 2009 Jan 16;1249:202-11. PubMed.
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