SOS1 and Ras regulate epithelial tight junction formation in the human airway through EMP1 Journal Article
| Authors: | Durgan, J.; Tao, G.; Walters, M. S.; Florey, O.; Schmidt, A.; Arbelaez, V.; Rosen, N.; Crystal, R. G.; Hall, A. |
| Article Title: | SOS1 and Ras regulate epithelial tight junction formation in the human airway through EMP1 |
| Abstract: | The human airway is lined with respiratory epithelial cells, which create a critical barrier through the formation of apical tight junctions. To investigate the molecular mechanisms underlying this process, an RNAi screen for guanine nucleotide exchange factors (GEFs) was performed in human bronchial epithelial cells (16HBE). We report that SOS1, acting through the Ras/MEK/ERK pathway, is essential for tight junction formation. Global microarray analysis identifies epithelial membrane protein 1 (EMP1), an integral tetraspan membrane protein, as a major transcriptional target. EMP1 is indispensable for tight junction formation and function in 16HBE cells and in a human airway basal progenitor-like cell line (BCi-NS1.1). Furthermore, EMP1 is significantly downregulated in human lung cancers. Together, these data identify important roles for SOS1/Ras and EMP1 in tight junction assembly during airway morphogenesis. Synopsis SOS1 and Ras promote the assembly of tight junctions in human bronchial epithelial cells by signaling through MEK and ERK. This controls the expression of EMP1, which is essential for tight junction formation and function in human airway epithelia. SOS1, Ras, MEK and ERK are required for proper tight junction assembly in bronchial epithelial cells. The ERK MAPK pathway controls the expression of multiple bronchial genes, including EMP1. EMP1 localises to tight junctions and is essential for their formation and function. SOS1 and Ras promote the assembly of tight junctions in human bronchial epithelial cells by signaling through MEK and ERK. This controls the expression of EMP1, which is essential for tight junction formation and function in human airway epithelia. © 2014 The Authors. |
| Keywords: | controlled study; protein expression; protein phosphorylation; unclassified drug; human cell; protein assembly; lung cancer; rna interference; uvomorulin; tight junction; microarray analysis; membrane protein; lung; cell count; ras protein; down regulation; ras; protein cdc42; cell contact; occludin; protein zo1; tight junctions; human; priority journal; article; emp1; sos1; claudin 1; epithelial membrane protein 1; sos protein; epithelium basal cell; lung alveolus epithelium cell |
| Journal Title: | EMBO Reports |
| Volume: | 16 |
| Issue: | 1 |
| ISSN: | 1469-221X |
| Publisher: | Wiley Blackwell |
| Date Published: | 2015-01-05 |
| Start Page: | 87 |
| End Page: | 96 |
| Language: | English |
| DOI: | 10.15252/embr.201439218 |
| PROVIDER: | scopus |
| PMCID: | PMC4304732 |
| PUBMED: | 25394671 |
| DOI/URL: | |
| Notes: | Export Date: 2 April 2015 -- Source: Scopus |
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