IQGAP1 is a MAPK cascade scaffolding protein that interacts with signalling and structural molecules. Although IQGAP1 has been implicated in the formation of adherens junctions, its role in the assembly and/or maintenance of tight junctions (TJs) has not previously been explored. In their study on page 853, Barbara Tanos, Enrique Rodriguez-Boulan and colleagues investigate, by using a systematic analysis, the effects of IQGAP1 knockdown on TJ formation and polarisation in the model MDCK cell line. The authors showed that RNAi-mediated inactivation of IQGAP1 promoted a transient increase in the transepithelial electrical resistance (TER), indicating that there is an increase in TJ-regulated paracellular permeability; this transient TER peak required actin polymerisation. Knockdown of IQGAP1 also decreased claudin 2 expression levels and recruitment to TJs, but enhanced claudin 4 recruitment, suggesting a mechanism for the peak in TER observed during TJ formation. Furthermore, the authors showed that IQGAP1 interacted with CDC42 (a known functional interactor of IQGAP1) during epithelial polarisation, and controlled TJ formation through transient inhibition of the CDC42–JNK pathway. These findings demonstrate a novel mechanism of TJ regulation by IQGAP1.

© 2015. Published by The Company of Biologists Ltd
2015