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mTORC2 suppresses cell death induced by hypo-osmotic stress by promoting sphingomyelin transport
The Journal of Cell Biology Pub Date : 2022-03-23 , DOI: 10.1083/jcb.202106160
Yumiko Ono 1 , Kenji Matsuzawa 1 , Junichi Ikenouchi 1
Affiliation  

Epithelial cells are constantly exposed to osmotic stress. The influx of water molecules into the cell in a hypo-osmotic environment increases plasma membrane tension as it rapidly expands. Therefore, the plasma membrane must be supplied with membrane lipids since expansion beyond its elastic limit will cause the cell to rupture. However, the molecular mechanism to maintain a constant plasma membrane tension is not known. In this study, we found that the apical membrane selectively expands when epithelial cells are exposed to hypo-osmotic stress. This requires the activation of mTORC2, which enhances the transport of secretory vesicles containing sphingomyelin, the major lipid of the apical membrane. We further show that the mTORC2–Rab35 axis plays an essential role in the defense against hypotonic stress by promoting the degradation of the actin cortex through the up-regulation of PI(4,5)P2 metabolism, which facilitates the apical tethering of sphingomyelin-loaded vesicles to relieve plasma membrane tension.

中文翻译:

mTORC2通过促进鞘磷脂转运抑制低渗应激诱导的细胞死亡

上皮细胞不断暴露于渗透压下。在低渗透压环境下,水分子流入细胞会随着细胞的快速扩张而增加质膜张力。因此,质膜必须提供膜脂,因为超出其弹性极限的扩张将导致细胞破裂。然而,维持恒定质膜张力的分子机制尚不清楚。在这项研究中,我们发现当上皮细胞暴露于低渗透压时,顶膜选择性地扩张。这需要激活 mTORC2,从而增强含有鞘磷脂(顶膜的主要脂质)的分泌囊泡的运输。我们进一步表明,mTORC2-Rab35 轴通过上调 PI(4,5)P2 代谢促进肌动蛋白皮质降解,从而促进鞘磷脂的顶端束缚,从而在防御低渗应激中发挥重要作用。负载囊泡以缓解质膜张力。
更新日期:2022-03-23
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