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SOS 1 and R as regulate epithelial tight junction formation in the human airway through EMP 1
Author(s) -
Durgan Joanne,
Tao Guangbo,
Walters Matthew S,
Florey Oliver,
Schmidt Anja,
Arbelaez Vanessa,
Rosen Neal,
Crystal Ronald G,
Hall Alan
Publication year - 2015
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201439218
Subject(s) - nobel laureate , cancer , library science , medicine , gerontology , art , computer science , literature , poetry
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 RNA i screen for guanine nucleotide exchange factors ( GEF s) was performed in human bronchial epithelial cells (16 HBE ). We report that SOS 1, acting through the Ras/ MEK / ERK pathway, is essential for tight junction formation. Global microarray analysis identifies epithelial membrane protein 1 ( EMP 1), an integral tetraspan membrane protein, as a major transcriptional target. EMP 1 is indispensable for tight junction formation and function in 16 HBE cells and in a human airway basal progenitor‐like cell line ( BC i‐ NS 1.1). Furthermore, EMP 1 is significantly downregulated in human lung cancers. Together, these data identify important roles for SOS 1/Ras and EMP 1 in tight junction assembly during airway morphogenesis.