Journal
JOURNAL OF CELL BIOLOGY
Volume 221, Issue 4, Pages -Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.202106160
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Funding
- JSPS KAKENHI [JP19H03227, JP21K19231, JP19K06640, JP20J10229]
- AMED-FORCE [21gm4010011h0001]
- JSTFOREST [JPMJFR204L]
- Mitsubishi Foundation
- Cell Science Research Foundation
- JSPS Research Fellowship for Young Scientists (DC2)
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This study reveals that epithelial cells selectively expand the apical membrane and maintain plasma membrane tension in hypo-osmotic stress through the activation of mTORC2-Rab35 axis, which enhances the transport of secretory vesicles containing major lipid to 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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