mTORC2 suppresses cell death induced by hypo-osmotic stress by promoting sphingomyelin transport.
mTORC2 suppresses cell death induced by hypo-osmotic stress by promoting sphingomyelin transport.
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DOI：
10.1083/jcb.202106160
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发表时间：
2022-04-04
期刊：
影响因子：
--
通讯作者：
Ikenouchi J
中科院分区：
文献类型：
--
作者：
Ono Y;Matsuzawa K;Ikenouchi J
Ono等人揭示，通过低渗应激激活mTORC 2-Rab 35不仅促进鞘磷脂向供应膜的顶端转运，而且通过减少PI（4，5）P2来减少顶膜下的肌动蛋白皮质，以促进顶膜的扩张。上皮细胞持续暴露于渗透压。在低渗透环境中，水分子涌入细胞，随着细胞迅速膨胀，细胞膜张力增加。因此，质膜必须有膜脂供应，因为超过其弹性极限的膨胀将导致细胞破裂。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应力时，顶膜选择性扩张。这需要mTORC 2的激活，其增强含有鞘磷脂（顶膜的主要脂质）的分泌囊泡的转运。我们进一步表明，mTORC 2-Rab 35轴通过PI（4，5）P2代谢的上调，促进肌动蛋白皮质的降解，从而在防御低渗应激中发挥重要作用，PI（4，5）P2代谢促进鞘磷脂负载囊泡的顶端束缚，以缓解质膜张力。
Ono et al. revealed that mTORC2–Rab35 activation by hypo-osmotic stress not only promotes apical transport of sphingomyelin to supply membrane but also decreases the actin cortex underlining the apical membrane by reducing PI(4,5)P2 to facilitate the expansion of the apical membrane. 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.
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影响因子：
7.7
作者：
Rai, Amrita;Oprisko, Anastasia;Mueller, Matthias P.
通讯作者：
Mueller, Matthias P.
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影响因子：
7.7
作者：
Muir A;Ramachandran S;Roelants FM;Timmons G;Thorner J
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Thorner J
PI（4,5）P2和其他肌醇磷脂对肌动蛋白组装的调节：可能的机制更新。
DOI：
10.1016/j.bbrc.2018.07.155
发表时间：
2018-11-25
影响因子：
3.1
作者：
Janmey PA;Bucki R;Radhakrishnan R
通讯作者：
Radhakrishnan R
DOI：
10.1101/sqb.1995.060.01.060
发表时间：
1995-01-01
期刊：
COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY
影响因子：
--
作者：
Dai, J;Sheetz, MP
通讯作者：
Sheetz, MP
DOI：
10.1083/jcb.201512024
发表时间：
2016-05-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Mrozowska PS;Fukuda M
通讯作者：
Fukuda M