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SMN Deficiency Reduces Cellular Ability to Form Stress Granules, Sensitizing Cells to Stress

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Abstract

Spinal Muscular Atrophy (SMA) is a neurodegenerative disease that is caused by deletion of the SMN (Survival of Motor Neuron) gene. The SMN protein is essential for cell survival and co-localized with TIA-1/R and G3BP, two characteristic markers of stress granules (SGs). To further study the SMN function in stress granules and in response to stress, we generated stable cell lines with SMN knockdown. Our data indicate that suppression of SMN drastically reduces cellular ability to form stress granules in response to stress treatment. In addition, we show that SMN deficiency sensitizes cells to sodium arsenite and H2O2, two well-known stress inducers, leading to cell death at a much lower concentration of inducers in SMN knockdown cells than in control cells. Interestingly, the cell death is correlated with formation of stress granules, suggesting that involvement of SMN in formation of stress granules may play an important role in cell survival. Furthermore, rescue of SGs formation by overexpression of G3BP can reverse the defective formation of stress granules and results in partial abrogation of cell death against SMN deficiency. We deduce that modulation of stress response may be useful for potential SMN treatment.

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Authors and Affiliations

  1. Jiangsu Key Laboratory of Neuroregeneration, Nantong University, 19th Qixiu Road, Nantong, JiangSu, 226007, People’s Republic of China

    Xianming Yang, Danmin Pan & Jianhua Zhou

  2. Department of Neurology, Children’s Hospital, Boston, MA, 02115, USA

    Jia Huang & Mustafa Sahin

  3. Department of Medicine, Program in Neuroscience, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA, 01605, USA

    Tie Zou & Jianhua Zhou

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  1. Tie Zou
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  2. Xianming Yang
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  3. Danmin Pan
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  4. Jia Huang
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  5. Mustafa Sahin
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  6. Jianhua Zhou
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Correspondence to Jianhua Zhou.

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Zou, T., Yang, X., Pan, D. et al. SMN Deficiency Reduces Cellular Ability to Form Stress Granules, Sensitizing Cells to Stress. Cell Mol Neurobiol 31, 541–550 (2011). https://doi.org/10.1007/s10571-011-9647-8

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  • DOI: https://doi.org/10.1007/s10571-011-9647-8

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