Cdc42 regulates apical junction formation in human bronchial epithelial cells through PAK4 and Par6B.

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Citation

Wallace SW, Durgan J, Jin D, Hall A

Cdc42 regulates apical junction formation in human bronchial epithelial cells through PAK4 and Par6B.

Mol Biol Cell. 2010 Sep 1;21(17):2996-3006. doi: 10.1091/mbc.E10-05-0429. Epub 2010 Jul 14.

PubMed ID
20631255 [ View in PubMed
]
Abstract

Cdc42 has been implicated in numerous biochemical pathways during epithelial morphogenesis, including the control of spindle orientation during mitosis, the establishment of apical-basal polarity, the formation of apical cell-cell junctions, and polarized secretion. To investigate the signaling pathways through which Cdc42 mediates these diverse effects, we have screened an siRNA library corresponding to the 36 known Cdc42 target proteins, in a human bronchial epithelial cell line. Two targets, PAK4 and Par6B, were identified as necessary for the formation of apical junctions. PAK4 is recruited to nascent cell-cell contacts in a Cdc42-dependent manner, where it is required for the maturation of primordial junctions into apical junctions. PAK4 kinase activity is essential for junction maturation, but overexpression of an activated PAK4 mutant disrupts this process. Par6B, together with its binding partner aPKC, is necessary both for junction maturation and for the retention of PAK4 at sites of cell-cell contact. This study demonstrates that controlled regulation of PAK4 is required for apical junction formation in lung epithelial cells and highlights potential cross-talk between two Cdc42 targets, PAK4 and Par6B.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Serine/threonine-protein kinase PAK 4O96013Details