IQGAP1 Controls Tight Junction Formation Through Differential Regulation of Claudin Recruitment Article (Web of Science)


  • IQGAP1 is a scaffolding protein previously implicated in adherens junction formation. However, its role in the establishment or maintenance of tight junctions (TJ) has not been explored. We hypothesized that IQGAP1 could regulate TJ formation by modulating the expression and/or localization of junctional proteins and systematically tested this hypothesis in the model cell line MDCK. We find that IQGAP1 silencing enhances a transient increase in transepithelial electrical resistance (TER) observed during early stages of TJ formation (Cereijido et al. 1978). Quantitative microscopy and biochemical experiments suggest that this effect of IQGAP1 on TJ assembly is accounted for by reduced expression and TJ recruitment of claudin 2, and increased TJ recruitment of claudin 4. Furthermore, we show that IQGAP1 also regulates TJ formation via its interactor CDC42 since IQGAP1 knockdown increases the activity of the CDC42 effector JNK and dominant negative CDC42 prevents the increase in TER caused by IQGAP1 silencing. Hence, we provide evidence that IQGAP1 modulates TJ formation by a two-fold mechanism: 1) controlling expression and recruitment of claudin 2 and claudin 4 recruitment to the TJ, and 2) transient inhibition of the CDC42-JNK pathway.


  • Tanos, Barbara E.
  • Perez-Bay, Andres
  • Salvarezza, Susana
  • Vivanco, Igor
  • Mellinghoff, Ingo
  • Osman, Mahasin
  • Sacks, David B.
  • Rodriguez-Boulan, Enrique

publication date

  • 2015

published in