Conversion of Zonulae Occludentes from Tight to Leaky Strand Type by Introducing Claudin-2 into Madin-Darby Canine Kidney I Cells

By M. Furuse, Kyoko Furuse, H. Sasaki, S. Tsukita. Journal of Cell Biology, 2001

738 citations recorded by the source corpus.

There are two strains of MDCK cells, MDCK I and II. MDCK I cells show much higher transepithelial electric resistance (TER) than MDCK II cells, although they bear similar numbers of tight junction (TJ) strands. We examined the expression pattern of claudins, the major components of TJ strands, in these cells: claudin-1 and -4 were expressed both in MDCK I and II cells, whereas the expression of claudin-2 was restricted to MDCK II cells. The dog claudin-2 cDNA was then introduced into MDCK I cells to mimic the claudin expression pattern of MDCK II cells. Interestingly, the TER values of MDCK I clones stably expressing claudin-2 (dCL2-MDCK I) fell to the levels of MDCK II cells (>20-fold decrease). In contrast, when dog claudin-3 was introduced into MDCK I cells, no change was detected in their TER. Similar results were obtained in mouse epithelial cells, Eph4. Morphometric analyses identified no significant differences in the density of TJs or in the number of TJ strands between dCL2-MDCK I and control MDCK I cells. These findings indicated that the addition of claudin-2 markedly decreased the tightness of individual claudin-1/4–based TJ strands, leading to the speculation that the combination and mixing ratios of claudin species determine the barrier properties of individual TJ strands.

Subfields: Molecular Biology, Neurology, Pediatrics, Perinatology and Child Health

View Paper: https://www.semanticscholar.org/paper/8610fb29659471c7b2825c573b37d13ab5a6d75d

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In Molecular Biology

1. J. Turner
2. Carola Förster
3. A. Buckley
4. R. Lynch
5. E. Schneeberger
6. C. V. Van Itallie
7. E. Dejana
8. A. Prat

In Neurology

1. J. Turner
2. Carola Förster
3. A. Buckley
4. R. Lynch
5. E. Schneeberger
6. C. V. Van Itallie
7. E. Dejana
8. A. Prat

Citations in the corpus

• Intestinal barrier function: molecular regulation and disease pathogenesis. (2009, result): “For example, introduction of claudin-2 into MDCK I cells that express claudin-1 and claudin-4 induces a decrease in transepithelial resistance (TER), whereas transfection of claudin-3 had no effect, suggesting that claudin-2 markedly decreased claudin-1/claudin-4–based TJ strand tightness.(88) In su”
• Tight junctions and the modulation of barrier function in disease (2008, background): “Major insight into the distinct charge selectivity of the claudins came from the work of Furuse et al. (2001), who could relate the diVerent levels of resistance between MDCK I cells (TER > 10,000 cm2) and MDCK II cells (TER <200 cm2) to a diVerential claudin isoform expression, while MDCK I cells…”
• Endothelial cell-to-cell junctions: molecular organization and role in vascular homeostasis. (2004, background): “Specifically, claudin-2 is absent in MDCK I but present in MDCK II (the strain with lower TER), and transfection of claudin-2 in MDCK I decreases TER to the levels observed in MDCK II (102).”
• Cytokine regulation of tight junctions (2008, background): “Increases in claudin 2 alter cell permeability, as exemplified by claudin 2 overexpression in epithelial cells, which lowers transepithelial resistance (TER) and confers increased Na+ conductance [63-65].”
• The tight junction: a multifunctional complex. (2004, background): “It also confirms indirectly the observations that claudin-2 forms cation-selective channels that are capable of changing a “tight” TJ to a leaky one (2, 48).”
• Physiology and function of the tight junction. (2009, background): “Claudins 2 (Furuse et al. 2001; Colegio et al. 2002; Amasheh et al. 2002) and 10 (Van Itallie et al. 2006) tend to make tight monolayers leakier.”
• Structure and function of claudins. (2008, neutral): “, carcinoma; CPE, Clostridium perfringens enterotoxin; ECL, extracellular loop; EphA2, receptor Tyr kinase; KO, knock out mice; LLC: LLC-PK1, renal epithelial cells of porcine proximal tubule (claudin-1, (-2), -3, -4, -7 [51]); MAPK, mitogen-activated protein kinase; MDCK, Madine–Darby canine kidney”
• Claudin-2 expression induces cation-selective channels in tight junctions of epithelial cells (2002, background): “Expression of claudin-2 decreases the overall transepithelial resistance in MDCK cells (Furuse et al., 2001).”
• The blood-brain barrier. (2015, background): “Expression of claudins is sufficient to form TJ strands in fibroblasts, and disruption of claudins decreases the paracellular barrier properties of canine kidney cells (Furuse et al. 1998, 2001; Van Itallie et al. 2001; Amasheh et al. 2005; Hou et al. 2006).”
• Tight junctions and cell polarity. (2006, background): “MDCK type II cells with low transepithelial resistance (TER) have a high level of claudin-2 expression, but MDCK type I cells with high TER express low levels of claudin-2 (Furuse et al. 2001).”