期刊
JOURNAL OF CELL BIOLOGY
卷 217, 期 7, 页码 2373-2381出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201711042
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资金
- Japan Society for the Promotion of Science KAKENHI [JP16H04786, JP16H01362, JP17H06012, JP16K14729, JP15KT0152, JP17J00211]
- Japan Agency for Medical Research and Development-PRIME [15664862]
- Japan Science and Technology Corporation-Precursory Research for Embryonic Science and Technology [JPM JPR12A4]
- MSD Life Science Foundation
- Takeda Science Foundation
- Japan Society for the Promotion of Science Research Fellowship for Young Scientists [DC1]
Tight junctions (TJs) are essential cell adhesion structures that act as a barrier to separate the internal milieu from the external environment in multicellular organisms. Although their major constituents have been identified, it is unknown how the formation of TJs is regulated. TJ formation depends on the preceding formation of adherens junctions (AJs) in epithelial cells; however, the underlying mechanism remains to be elucidated. In this study, loss of AJs in alpha-catenin-knockout (KO) EpH4 epithelial cells altered the lipid composition of the plasma membrane (PM) and led to endocytosis of claudins, a major component of TJs. Sphingomyelin with long-chain fatty acids and cholesterol were enriched in the TJ-containing PM fraction. Depletion of cholesterol abolished the formation of TJs. Conversely, addition of cholesterol restored TJ formation in alpha-catenin-KO cells. Collectively, we propose that AJs mediate the formation of TJs by increasing the level of cholesterol in the PM.
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