A peculiar internalization of claudins, tight junction-specific adhesion molecules, during the intercellular movement of epithelial cells

Miho Matsuda, Akiharu Kubo, Mikio Furuse, Shoichiro Tsukita

Research output: Contribution to journalArticle

170 Citations (Scopus)

Abstract

Tight junctions (TJs) seal the intercellular space of epithelial cells, while individual epithelial cells move against adjacent cells in cellular sheets. To observe TJs in live epithelial cellular sheets, green fluorescent protein (GFP) was fused to the N-terminus of claudin-3 (a major cell adhesion molecule of TJs), which was stably expressed at a level that was approximately 50% of that of endogenous claudin-3 in mouse Eph4 epithelial cells. Under confluent culture conditions, individual cells moved within cellular sheets, which was associated with the remodeling of TJs. However, during this remodeling, GFP-positive TJs did not lose their structural continuity. When TJs between two adjacent cells decreased in length during this remodeling, GFP-claudin-3 was frequently pinched off as a granular structure from GFP-positive TJs together with endogenous claudins. Co-culture experiments, as well as electron microscopy, revealed that the two apposed membranes of TJs were not detached, but co-endocytosed into one of the adjacent cells. Interestingly, other TJ components such as occludin, JAM and ZO-1 appeared to be dissociated from claudins before this endocytosis. The endocytosis of claudins was facilitated when the intercellular motility was upregulated by wounding the cellular sheets. These findings suggest that this peculiar internalization of claudins plays a crucial role in the remodeling of TJs, and that the fine regulation of this endocytosis is important for TJs to seal the intercellular space of epithelial cells that are moving against adjacent cells within cellular sheets.

Original languageEnglish
Pages (from-to)1247-1257
Number of pages11
JournalJournal of Cell Science
Volume117
Issue number7
DOIs
Publication statusPublished - 2004 Mar 1
Externally publishedYes

Fingerprint

Junctional Adhesion Molecules
Claudins
Tight Junctions
Epithelial Cells
Claudin-3
Endocytosis
Green Fluorescent Proteins
Extracellular Space
Occludin
Cell Adhesion Molecules
Coculture Techniques

Keywords

  • Claudin
  • Intercellular motility
  • Internalization
  • Tight junction
  • ZO-1

ASJC Scopus subject areas

  • Cell Biology

Cite this

A peculiar internalization of claudins, tight junction-specific adhesion molecules, during the intercellular movement of epithelial cells. / Matsuda, Miho; Kubo, Akiharu; Furuse, Mikio; Tsukita, Shoichiro.

In: Journal of Cell Science, Vol. 117, No. 7, 01.03.2004, p. 1247-1257.

Research output: Contribution to journalArticle

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