LSR defines cell corners for tricellular tight junction formation in epithelial cells.
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.
Division of Cell Biology, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
Sayuri
S
Masuda
Yukako
Y
Oda
Hiroyuki
H
Sasaki
Junichi
J
Ikenouchi
Tomohito
T
Higashi
Masaya
M
Akashi
Eiichiro
E
Nishi
Mikio
M
Furuse
D000818:Animals; D045744:Cell Line, Tumor; D004285:Dogs; D004847:Epithelial Cells / Q000737:chemistry / Q000378:metabolism*; D005110:Extracellular Space / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D062794:MARVEL Domain Containing 2 Protein; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011973:Receptors, LDL / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019108:Tight Junctions / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D062794:MARVEL Domain Containing 2 Protein; C516798:MARVELD2 protein, human; D008565:Membrane Proteins; D011973:Receptors, LDL; C085992:lipolysis-stimulated receptor