Membrane lipid saturation activates IRE1α without inducing clustering

Genes to Cells - Tập 18 Số 9 - Trang 798-809 - 2013
Yuto Kitai1, Hiroyuki Ariyama1, Nozomu Kono2,1, Daisuke Oikawa3, Takao Iwawaki3, Hiroyuki Arai2,1
1Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan
2Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan
3Iwawaki Laboratory, Advanced Scientific Research Leaders Development Unit, Gunma University, Maebashi, Gunma, 371-8511 Japan

Tóm tắt

The unfolded protein response (UPR) is an adaptive stress response that responds to the accumulation of unfolded proteins in the lumen of the endoplasmic reticulum (ER) and that adjusts the protein‐folding capacity to the needs of the cell. Perturbation of cellular lipids also activates the UPR. Lipid‐induced UPR has attracted much attention because it is associated with the pathology of some metabolic diseases. However, how the lipid‐induced UPR is activated remains unclear. We previously showed that palmitic acid treatment or knockdown of stearoyl‐CoA desaturase in HeLa cells promotes membrane lipid saturation and activates the UPR. In this study, we compared UPR activation by membrane lipid saturation with UPR activation by conventional ER stressors that cause the accumulation of unfolded proteins such as tunicamycin and thapsigargin. Membrane lipid saturation induced autophosphorylation of inositol‐requiring 1α (IRE1α) and protein kinase RNA‐like ER kinase, but not the conversion of activating transcription factor‐6α to the active form. A conventional ER stressor induced clustering of fluorescently tagged IRE1α fusion protein, but palmitic acid treatment did not, suggesting that IRE1α was activated without large cluster formation by membrane lipid saturation. Together, these results suggest membrane lipid saturation, and unfolded proteins activate the UPR through different mechanisms.

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Genes to Cells

Tập 18 Số 9

798-809

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