Adherens junctions influence tight junction formation via changes in membrane lipid composition

Kenta Shigetomi, Yumiko Ono, Tetsuichiro Inai, Junichi Ikenouchi

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

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 α-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 α-catenin-KO cells. Collectively, we propose that AJs mediate the formation of TJs by increasing the level of cholesterol in the PM.

Original languageEnglish
Pages (from-to)2373-2381
Number of pages9
JournalJournal of Cell Biology
Volume217
Issue number7
DOIs
Publication statusPublished - Jul 2018

All Science Journal Classification (ASJC) codes

  • Cell Biology

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