LSR defines cell corners for tricellular tight junction formation in epithelial cells

Sayuri Masuda, Yukako Oda, Hiroyuki Sasaki, Junichi Ikenouchi, Tomohito Higashi, Masaya Akashi, Eiichiro Nishi, Mikio Furuse

Research output: Contribution to journalArticlepeer-review

140 Citations (Scopus)

Abstract

Epithelial cell contacts consist of not only bicellular contacts but also tricellular contacts, where the corners of three cells meet. At tricellular contacts, tight junctions (TJs) generate specialized structures termed tricellular TJs (tTJs) to seal the intercellular space. Tricellulin is the only known molecular component of tTJs and is involved in the formation of tTJs, as well as in the normal epithelial barrier function. However, the detailed molecular mechanism of how tTJs are formed and maintained remains elusive. Using a localization-based expression cloning method, we identified a novel tTJ-associated protein known as lipolysis-stimulated lipoprotein receptor (LSR). Upon LSR knockdown in epithelial cells, tTJ formation was affected and the epithelial barrier function was diminished. Tricellulin accumulation at the tricellular contacts was also diminished in these cells. By contrast, LSR still accumulated at the tricellular contacts upon tricellulin knockdown. Analyses of deletion mutants revealed that the cytoplasmic domain of LSR was responsible for the recruitment of tricellulin. On the basis of these observations, we propose that LSR defines tricellular contacts in epithelial cellular sheets by acting as a landmark to recruit tricellulin for tTJ formation.

Original languageEnglish
Pages (from-to)548-555
Number of pages8
JournalJournal of cell science
Volume124
Issue number4
DOIs
Publication statusPublished - Feb 15 2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cell Biology

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