SOS1 and Ras regulate epithelial tight junction formation in the human airway through EMP1

Joanne Durgan, Guangbo Tao, Matthew S. Walters, Oliver Florey, Anja Schmidt, Vanessa Arbelaez, Neal Rosen, Ronald Crystal, Alan Hall

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)87-96
Number of pages10
JournalEMBO Reports
Volume16
Issue number1
DOIs
Publication statusPublished - 1 Jan 2015
Externally publishedYes

Fingerprint

Tight Junctions
Mitogen-Activated Protein Kinase Kinases
Epithelial Cells
MAP Kinase Signaling System
Guanine Nucleotide Exchange Factors
Epithelium
epithelial membrane protein-1
Microarrays
Microarray Analysis
Membrane Proteins
RNA Interference
Morphogenesis
Genes
Cells
Lung Neoplasms
Stem Cells
Down-Regulation
Cell Line

Keywords

  • EMP1
  • lung
  • Ras
  • SOS1
  • tight junctions

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Biochemistry
  • Medicine(all)

Cite this

Durgan, J., Tao, G., Walters, M. S., Florey, O., Schmidt, A., Arbelaez, V., ... Hall, A. (2015). SOS1 and Ras regulate epithelial tight junction formation in the human airway through EMP1. EMBO Reports, 16(1), 87-96. https://doi.org/10.15252/embr.201439218

SOS1 and Ras regulate epithelial tight junction formation in the human airway through EMP1. / Durgan, Joanne; Tao, Guangbo; Walters, Matthew S.; Florey, Oliver; Schmidt, Anja; Arbelaez, Vanessa; Rosen, Neal; Crystal, Ronald; Hall, Alan.

In: EMBO Reports, Vol. 16, No. 1, 01.01.2015, p. 87-96.

Research output: Contribution to journalArticle

Durgan, J, Tao, G, Walters, MS, Florey, O, Schmidt, A, Arbelaez, V, Rosen, N, Crystal, R & Hall, A 2015, 'SOS1 and Ras regulate epithelial tight junction formation in the human airway through EMP1', EMBO Reports, vol. 16, no. 1, pp. 87-96. https://doi.org/10.15252/embr.201439218
Durgan J, Tao G, Walters MS, Florey O, Schmidt A, Arbelaez V et al. SOS1 and Ras regulate epithelial tight junction formation in the human airway through EMP1. EMBO Reports. 2015 Jan 1;16(1):87-96. https://doi.org/10.15252/embr.201439218
Durgan, Joanne ; Tao, Guangbo ; Walters, Matthew S. ; Florey, Oliver ; Schmidt, Anja ; Arbelaez, Vanessa ; Rosen, Neal ; Crystal, Ronald ; Hall, Alan. / SOS1 and Ras regulate epithelial tight junction formation in the human airway through EMP1. In: EMBO Reports. 2015 ; Vol. 16, No. 1. pp. 87-96.
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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.",
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