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Publication : The Endosomal Protein Endotubin Is Required for Enterocyte Differentiation.

First Author  Cox CM Year  2018
Journal  Cell Mol Gastroenterol Hepatol Volume  5
Issue  2 Pages  145-156
PubMed ID  29322087 Mgi Jnum  J:322247
Mgi Id  MGI:7257881 Doi  10.1016/j.jcmgh.2017.11.001
Citation  Cox CM, et al. (2018) The Endosomal Protein Endotubin Is Required for Enterocyte Differentiation. Cell Mol Gastroenterol Hepatol 5(2):145-156
abstractText  BACKGROUND & AIMS: During late embryonic development and through weaning, enterocytes of the ileum are highly endocytic. Defects in endocytosis and trafficking are implicated in neonatal disease, however, the mechanisms regulating trafficking during the developmental period are incompletely understood. The apical endosomal protein endotubin (EDTB) is highly expressed in the late embryonic and neonatal ileum. In epithelial cells in vitro, EDTB regulates both trafficking of tight junction proteins and proliferation through modulation of YAP activity. However, EDTB function during the endocytic stage of development of the intestine is unknown. METHODS: By using Villin-CreERT2, we induced knockout of EDTB during late gestation and analyzed the impact on endocytic compartments and enterocyte structure in neonates using immunofluorescence, immunocytochemistry, and transmission electron microscopy. RESULTS: Deletion of the apical endosomal protein EDTB in the small intestine during development impairs enterocyte morphogenesis, including loss of the apical endocytic complex, defective formation of the lysosomal compartment, and some cells had large microvillus-rich inclusions similar to those observed in microvillus inclusion disease. There also was a decrease in apical endocytosis and mislocalization of proteins involved in apical trafficking. CONCLUSIONS: Our results show that EDTB-mediated trafficking within the epithelial cells of the developing ileum is important for maintenance of endocytic compartments and enterocyte integrity during early stages of gut development.
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