Cdc42 Regulates Apical Junction Formation in Human Bronchial Epithelial Cells through PAK4 and Par6B

Wallace, Sean W.; Durgan, Joanne; Jin, Dan; Hall, Alan

doi:10.1091/mbc.e10-05-0429

Cited by 63 publications

(90 citation statements)

References 55 publications

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“…The apical junctional complex of epithelial cells consists of tight junctions, adherens junctions, and the associated perijunctional actin ring. We have previously described the mechanism of apical junction formation in 16HBE cells by using a calcium switch to induce junction formation (42). Confluent monolayers of 16HBE cells were incubated in low-calcium medium to disassemble junctions, followed by the addition of calcium to stimulate junction formation.…”

Section: Resultsmentioning

confidence: 99%

“…We recently described two additional serine-threonine kinases required for the formation of mature apical junctions in 16HBE cells, PAK4 and aPKC, both Cdc42 targets (42). Depletion of PRK2, PAK4, or aPKC leads to an apparently identical phenotype in which cells undergo the initial step of junction formation to form primordial junctions but these do not mature into apical junctions.…”

Section: Discussionmentioning

confidence: 99%

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The Rho Target PRK2 Regulates Apical Junction Formation in Human Bronchial Epithelial Cells

Wallace

Magalhaes

Hall

2011

Molecular and Cellular Biology

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Rho GTPases regulate multiple signaling pathways to control a number of cellular processes during epithelial morphogenesis. To investigate the downstream pathways through which Rho regulates epithelial apical junction formation, we screened a small interfering RNA (siRNA) library targeting 28 known Rho target proteins in 16HBE human bronchial epithelial cells. This led to the identification of the serine-threonine kinase PRK2 (protein kinase C-related kinase 2, also called PKN2). Depletion of PRK2 does not block the initial formation of primordial junctions at nascent cell-cell contacts but does prevent their maturation into apical junctions. PRK2 is recruited to primordial junctions, and this localization depends on its C2-like domain. Rho binding is essential for PRK2 function and also facilitates PRK2 recruitment to junctions. Kinase-dead PRK2 acts as a dominant-negative mutant and prevents apical junction formation. We conclude that PRK2 is recruited to nascent cell-cell contacts through its C2-like and Rho-binding domains and promotes junctional maturation through a kinase-dependent pathway.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Rho Target PRK2 Regulates Apical Junction Formation in Human Bronchial Epithelial Cells

Wallace

Magalhaes

Hall

2011

Molecular and Cellular Biology

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“…In endothelial cells and C.elegans, p120 CTN may also dynamically modulate contractility at the lateral domains via its interaction with RhoA upstream regulators [65,66]. PAK family members, serine threonine kinases effectors of Rac1 and Cdc42 GTPase known to modulate contraction [67], could also participate: either via transiently activation by cell-cell contact formation (PAK1) [68] or localization at epithelial junctions (PAK4 and PAK6) [69][70][71][72].…”

Section: Thin Bundles and The Regulation Of Lateral Height And Junctimentioning

confidence: 99%

Spatial integration of E-cadherin adhesion, signalling and the epithelial cytoskeleton

Braga

2016

Current Opinion in Cell Biology

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“…However, IQGAP1 can also regulate the activation of CDC42 (Rittmeyer et al, 2008). CDC42 is also required for TJ formation (Wallace et al, 2010) and maintenance (Rojas et al, 2001). To investigate the relevance of the IQGAP1-CDC42 interaction in the regulation of TJ formation, we examined their physical association during epithelial cell polarization.…”

Section: Transient Ter Peak Requires Actin Polymerizationmentioning

confidence: 99%

IQGAP1 Controls Tight Junction Formation Through Differential Regulation of Claudin Recruitment

Tanos

Bay

Salvarezza

et al. 2015

Journal of Cell Science

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IQGAP1 is a scaffolding protein previously implicated in adherens junction formation. However, its role in the establishment or maintenance of tight junctions (TJs) has not been explored. We hypothesized that IQGAP1 could regulate TJ formation by modulating the expression and/or localization of junctional proteins, and we systematically tested this hypothesis in the model Madin-Darby canine kidney (MDCK) cell line. We find that IQGAP1 silencing enhances a transient increase in transepithelial electrical resistance (TER) observed during the 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 through its interactor CDC42, because IQGAP1 knockdown increases the activity of the CDC42 effector JNK and dominantnegative CDC42 prevents the increase in TER caused by IQGAP1 silencing. Hence, we provide evidence that IQGAP1 modulates TJ formation by a twofold mechanism: (1) controlling the expression and recruitment of claudin 2 and recruitment of claudin 4 to the TJ, and (2) transient inhibition of the CDC42-JNK pathway.

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Cdc42 Regulates Apical Junction Formation in Human Bronchial Epithelial Cells through PAK4 and Par6B

Cited by 63 publications

References 55 publications

The Rho Target PRK2 Regulates Apical Junction Formation in Human Bronchial Epithelial Cells

The Rho Target PRK2 Regulates Apical Junction Formation in Human Bronchial Epithelial Cells

Spatial integration of E-cadherin adhesion, signalling and the epithelial cytoskeleton

IQGAP1 Controls Tight Junction Formation Through Differential Regulation of Claudin Recruitment

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