The Endosomal Protein Endotubin Is Required for Enterocyte Differentiation

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.

• Publication year

  2017

• Venue

  Cellular and Molecular Gastroenterology and Hepatology

• Publication date

  2017-11-15

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/j.jcmgh.2017.11.001PMID 29322087PMCID 5756061
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Disruption of Rab8a and Rab11a causes formation of basolateral microvilli in neonatal enteropathy

  2017cited by this paper
• The role of enterocyte defects in the pathogenesis of congenital diarrheal disorders

  2016cited by this paper
• Tight junctions in inflammatory bowel diseases and inflammatory bowel disease associated colorectal cancer.

  2016cited by this paper
• Intestinal barrier dysfunction in human necrotizing enterocolitis.

  2016cited by this paper
• Rab14 specifies the apical membrane through Arf6-mediated regulation of lipid domains and Cdc42

  2016cited by this paper
• Postnatal regulation of MAMDC4 in the porcine intestinal epithelium is influenced by bacterial colonization

  2016cited by this paper
• The Arp2/3 complex has essential roles in vesicle trafficking and transcytosis in the mammalian small intestine

  2015cited by this paper
• An inducible mouse model for microvillus inclusion disease reveals a role for myosin Vb in apical and basolateral trafficking

  2015cited by this paper
• Endosomal regulation of contact inhibition through the AMOT:YAP pathway

  2015cited by this paper
• Rab11a regulates syntaxin 3 localization and microvillus assembly in enterocytes

  2015cited by this paper
• PKCι interacts with Rab14 and modulates epithelial barrier function through regulation of claudin-2 levels

  2015cited by this paper
• Loss of MYO5B in Mice Recapitulates Microvillus Inclusion Disease and Reveals an Apical Trafficking Pathway Distinct to Neonatal Duodenum

  2015cited by this paper
• Claudin-1 overexpression in intestinal epithelial cells enhances susceptibility to adenamatous polyposis coli-mediated colon tumorigenesis

  2014cited by this paper
• Myosin Vb uncoupling from RAB8A and RAB11A elicits microvillus inclusion disease.

  2014cited by this paper
• Rab11a is required for apical protein localisation in the intestine

  2014cited by this paper
• Rab8a and Rab8b are essential for several apical transport pathways but insufficient for ciliogenesis

  2014cited by this paper
• Rab14 regulation of claudin-2 trafficking modulates epithelial permeability and lumen morphogenesis

  2014cited by this paper
• Myosin 5b loss of function leads to defects in polarized signaling: implication for microvillus inclusion disease pathogenesis and treatment.

  2014cited by this paper
• Loss of syntaxin 3 causes variant microvillus inclusion disease.

  2014cited by this paper
• A role for Rab14 in the endocytic trafficking of GLUT4 in 3T3-L1 adipocytes

  2013cited by this paper
• Specialized sorting of GLUT4 and its recruitment to the cell surface are independently regulated by distinct Rabs

  2013cited by this paper
• Cdc42 coordinates proliferation, polarity, migration, and differentiation of small intestinal epithelial cells in mice.

  2013cited by this paper
• Cdc42 and Rab8a are critical for intestinal stem cell division, survival, and differentiation in mice.

  2012cited by this paper
• KIF16B/Rab14 molecular motor complex is critical for early embryonic development by transporting FGF receptor.

  2011cited by this paper
• Blimp1 regulates the transition of neonatal to adult intestinal epithelium

  2011cited by this paper
• Regulation of Tight Junction Assembly and Epithelial Polarity by a Resident Protein of Apical Endosomes

  2010cited by this paper
• Cdx2 regulates endo-lysosomal function and epithelial cell polarity.

  2010cited by this paper
• Establishment of intestinal identity and epithelial-mesenchymal signaling by Cdx2.

  2009cited by this paper
• Navajo microvillous inclusion disease is due to a mutation in MYO5B

  2008cited by this paper
• Rab14 Regulates Apical Targeting in Polarized Epithelial Cells

  2008cited by this paper
• MYO5B mutations cause microvillus inclusion disease and disrupt epithelial cell polarity

  2008cited by this paper
• The Rab8 GTPase regulates apical protein localization in intestinal cells

  2007cited by this paper
• Intracellular bacterial growth is controlled by a kinase network around PKB/AKT1

  2007cited by this paper
• Bile acids induce ileal damage during experimental necrotizing enterocolitis.

  2006cited by this paper
• Disordered enterocyte signaling and intestinal barrier dysfunction in the pathogenesis of necrotizing enterocolitis.

  2005cited by this paper
• Rab14 is involved in membrane trafficking between the Golgi complex and endosomes.

  2004cited by this paper
• EEA1, a tethering protein of the early sorting endosome, shows a polarized distribution in hippocampal neurons, epithelial cells, and fibroblasts.

  2000cited by this paper
• Identification of a Marker Antigen for the Endocytic Stage of Intestinal Development in Rat, Sheep, and Human

  1995cited by this paper
• Biogenesis of the apical endosome-lysosome complex during differentiation of absorptive epithelial cells in rat ileum.

  1991influential reference
• Transepithelial transport of epidermal growth factor by absorptive cells of suckling rat ileum.

  1987cited by this paper
• Identification of an endosomal antigen specific to absorptive cells of suckling rat ileum

  1987cited by this paper
• Uptake and transepithelial transport of nerve growth factor in suckling rat ileum

  1986cited by this paper
• Glycoconjugate distribution and mobility on apical membranes of absorptive cells of suckling rat ileum in vivo

  1985cited by this paper
• Membrane-bound and fluid-phase macromolecules enter separate prelysosomal compartments in absorptive cells of suckling rat ileum

  1984cited by this paper
• In vitro determination of small intestinal permeability: demonstration of a persistent defect in patients with coeliac disease.

  1984cited by this paper
• REGULAR STRUCTURES IN MEMBRANES

  1974cited by this paper
• I. Membranes in the Endocytic Complex of Ileal Epithelial Cells

  1974cited by this paper
• MEMBRANE MODIFICATIONS IN THE APICAL ENDOCYTIC COMPLEX OF ILEAL EPITHELIAL CELLS

  1968cited by this paper

• The mouse neonatal small intestine is regionally specialized for protein absorption and transepithelial transport

  2025cites this paper
• Rab14 promotes Parkin mediated mitophagy.

  2025cites this paper
• Protective Effect of IgY Embedded in W/O/W Emulsion on LPS Enteritis-Induced Colonic Injury in Mice

  2024cites this paper
• Myosin Vb Traffics P-glycoprotein to the Apical Membrane of Intestinal Epithelial Cells.

  2024cites this paper
• Regulation of YAP and Wnt signaling by the endosomal protein MAMDC4

  2024cites this paper
• Amelioration of LPS-Induced Jejunum Injury and Mucus Barrier Damage in Mice by IgY Embedded in W/O/W Emulsion

  2024cites this paper
• Modeling the cell biology of monogenetic intestinal epithelial disorders.

  2024cites this paper
• Altered MYO5B Function Underlies Microvillus Inclusion Disease: Opportunities for Intervention at a Cellular Level

  2022cites this paper
• Morphological and molecular features of early regeneration in the marine annelid Ophryotrocha xiamen

  2022cites this paper
• Maf family transcription factors are required for nutrient uptake in the mouse neonatal gut.

  2022cites this paper
• Recruitment of Polarity Complexes and Tight Junction Proteins to the Site of Apical Bulk Endocytosis

  2021cites this paper
• Proliferation in the developing intestine is regulated by the endosomal protein Endotubin.

  2021cites this paper
• A Comprehensive Ultrastructure and Transcriptome Analyses of Early Regeneration in Ophryotrocha Xiamen Sp. Nov. (Annelida: Dorvilleidae)

  2020cites this paper
• Astragalus polysaccharides alleviates LPS‐induced inflammation via the NF‐κB/MAPK signaling pathway

  2020cites this paper
• Loss of myosin Vb promotes apical bulk endocytosis in neonatal enterocytes

  2019cites this paper
• Loss of MYO5B Leads to Reductions in Na+ Absorption With Maintenance of CFTR-Dependent Cl- Secretion in Enterocytes.

  2018cites this paper
• Formation of Giant Lysosome in Neonatal Ileal Enterocytes Requires Endotubin

  2017cites this paper