Occludin S471 Phosphorylation Contributes to Epithelial Monolayer Maturation.
Mol Cell Biol
; 36(15): 2051-66, 2016 08 01.
Article
em En
| MEDLINE
| ID: mdl-27185880
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Serina
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Junções Íntimas
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Células Epiteliais
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Quinases de Receptores Acoplados a Proteína G
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Ocludina
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article