Abstract:
:Multiple organ systems require epithelial barriers for normal function, and barrier loss is a hallmark of diseases ranging from inflammation to epithelial cancers. However, the molecular processes regulating epithelial barrier maturation are not fully elucidated. After contact, epithelial cells undergo size-reductive proliferation and differentiate, creating a dense, highly ordered monolayer with high resistance barriers. We provide evidence that the tight junction protein occludin contributes to the regulation of epithelial cell maturation upon phosphorylation of S471 in its coiled-coil domain. Overexpression of a phosphoinhibitory occludin S471A mutant prevents size-reductive proliferation and subsequent tight junction maturation in a dominant manner. Inhibition of cell proliferation in cell-contacted but immature monolayers recapitulated this phenotype. A kinase screen identified G-protein-coupled receptor kinases (GRKs) targeting S471, and GRK inhibitors delayed epithelial packing and junction maturation. We conclude that occludin contributes to the regulation of size-reductive proliferation and epithelial cell maturation in a phosphorylation-dependent manner.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Bolinger MT,Ramshekar A,Waldschmidt HV,Larsen SD,Bewley MC,Flanagan JM,Antonetti DAdoi
10.1128/MCB.00053-16subject
Has Abstractpub_date
2016-07-14 00:00:00pages
2051-66issue
15eissn
0270-7306issn
1098-5549pii
MCB.00053-16journal_volume
36pub_type
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